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Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

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ClinicalTrials.gov Identifier: NCT02465060
Recruitment Status : Recruiting
First Posted : June 8, 2015
Last Update Posted : September 22, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE June 3, 2015
First Posted Date  ICMJE June 8, 2015
Last Update Posted Date September 22, 2021
Actual Study Start Date  ICMJE August 12, 2015
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2019)		 Objective response rate [ Time Frame: Up to 3 years ]
Defined as the percentage of patients whose tumors have a complete or partial response to treatment. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided confidence intervals will be calculated.
Original Primary Outcome Measures  ICMJE
 (submitted: June 3, 2015)		 Objective response rate (ORR), defined as a complete or partial response [ Time Frame: Up to 3 years ]
ORR is defined consistent with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology (RANO) criteria for GBM patients. For each arm, 80% two-sided confidence intervals for the ORR will be calculated.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2020)
  • Overall survival [ Time Frame: From registration onto that step until death, or censored at the date of last contact, assessed up to 3 years ]
    Will be evaluated specifically for each drug (or step). Overall survival will be estimated using the Kaplan-Meier method.
  • Progression free survival [ Time Frame: From entry onto that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months ]
    Progression free survival will be estimated using the Kaplan-Meier method. For each treatment arm, 90% two-sided confidence intervals will be calculated.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2015)
  • Overall survival (OS), evaluated specifically for each drug (or step) [ Time Frame: From registration onto that step until death, or censored at the date of last contact, assessed up to 3 years ]
    OS will be estimated using the Kaplan-Meier method.
  • Progression free survival (PFS) [ Time Frame: From entry onto that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months ]
    PFS will be estimated using the Kaplan-Meier method.
  • Time to progression (TTP) [ Time Frame: From entry to that step until determination of disease progression or death due to disease, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years ]
    TTP will be estimated using the Kaplan-Meier method.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: June 3, 2015)
  • Biomarkers that provide clues for mechanisms of acquired resistance [ Time Frame: Up to 3 years ]
    Biomarkers measured at time of progression might provide clues for mechanisms of acquired resistance. Changes in biomarker levels from baseline (prior to receiving the treatment) to progression within patients will be assessed using paired tests appropriate for the type of biomarker measurement (e.g., paired t-tests for normally distributed biomarker values or McNemar tests for paired binary data). It will also be assessed whether patterns of changes in biomarkers are different depending on length of time to progression.
  • Potential predictive biomarkers beyond the genomic alteration [ Time Frame: Baseline ]
    Biomarkers measured prior to treatment could be predictive of response or non-response to the agent. Analyses conducted to identify predictive biomarkers will be primarily exploratory and will consist of simple comparisons of biomarkers levels, either using binomial-based tests (for binary biomarkers), t-tests (continuous biomarkers, possibly transformed), or non-parametric tests, as appropriate depending on the distribution of the biomarker values.
 
Descriptive Information
Brief Title  ICMJE Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Official Title  ICMJE Molecular Analysis for Therapy Choice (MATCH)
Brief Summary This phase II MATCH trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.
Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

STEP 0 (Screening): Patients undergo biopsy along with molecular characterization of the biopsy material for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing and immunohistochemistry. Consenting patients also undergo collection of blood samples for research purposes.

STEPS 1, 3, 5, 7 (Treatment): Patients are assigned to 1 of 38 treatment subprotocols based on molecularly-defined subgroup. (See Arms Section)

STEPS 2, 4, 6 (Screening): Patients experiencing disease progression on the prior Step treatment or who could not tolerate the assigned treatment undergo review of their previous biopsy results to determine if another treatment is available or undergo another biopsy. Patients may have a maximum of 2 screening biopsies and 2 treatments per biopsy.

STEP 8 (Optional Research): Consenting patients undergo end-of-treatment biopsy and collection of blood samples for research purposes.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Malignant Solid Neoplasm
  • Bladder Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colon Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Glioma
  • Head and Neck Carcinoma
  • Kidney Carcinoma
  • Liver and Intrahepatic Bile Duct Carcinoma
  • Lung Carcinoma
  • Lymphoma
  • Malignant Uterine Neoplasm
  • Melanoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Plasma Cell Myeloma
  • Prostate Carcinoma
  • Rectal Carcinoma
  • Recurrent Bladder Carcinoma
  • Recurrent Breast Carcinoma
  • Recurrent Cervical Carcinoma
  • Recurrent Colon Carcinoma
  • Recurrent Colorectal Carcinoma
  • Recurrent Esophageal Carcinoma
  • Recurrent Gastric Carcinoma
  • Recurrent Glioma
  • Recurrent Head and Neck Carcinoma
  • Recurrent Liver Carcinoma
  • Recurrent Lung Carcinoma
  • Recurrent Lymphoma
  • Recurrent Malignant Solid Neoplasm
  • Recurrent Melanoma
  • Recurrent Ovarian Carcinoma
  • Recurrent Pancreatic Carcinoma
  • Recurrent Plasma Cell Myeloma
  • Recurrent Prostate Carcinoma
  • Recurrent Rectal Carcinoma
  • Recurrent Skin Carcinoma
  • Recurrent Thyroid Gland Carcinoma
  • Recurrent Uterine Corpus Cancer
  • Refractory Lymphoma
  • Refractory Malignant Solid Neoplasm
  • Refractory Plasma Cell Myeloma
  • Skin Carcinoma
  • Thyroid Gland Carcinoma
  • Uterine Corpus Cancer
Intervention  ICMJE
  • Drug: Adavosertib
    Given PO
    Other Names:
    • AZD-1775
    • AZD1775
    • MK-1775
    • MK1775
  • Drug: Afatinib
    Given PO
    Other Names:
    • BIBW 2992
    • BIBW2992
  • Drug: Afatinib Dimaleate
    Given PO
    Other Names:
    • (2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
    • BIBW 2992MA2
    • BIBW2992 MA2
    • Gilotrif
  • Drug: Binimetinib
    Given PO
    Other Names:
    • ARRY-162
    • ARRY-438162
    • MEK162
    • Mektovi
  • Drug: Capivasertib
    Given PO
    Other Name: AZD5363
  • Drug: Copanlisib
    Given IV
    Other Names:
    • BAY 80-6946
    • PI3K Inhibitor BAY 80-6946
  • Drug: Copanlisib Hydrochloride
    Given IV
    Other Names:
    • 5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2)
    • Aliqopa
    • BAY 80-6946 Dihydrochloride
    • BAY-80-6946 Dihydrochloride
    • Copanlisib Dihydrochloride
  • Drug: Crizotinib
    Given PO
    Other Names:
    • MET Tyrosine Kinase Inhibitor PF-02341066
    • PF-02341066
    • PF-2341066
    • Xalkori
  • Other: Cytology Specimen Collection Procedure
    Optional correlative studies
    Other Name: Cytologic Sampling
  • Drug: Dabrafenib
    Given PO
    Other Names:
    • BRAF Inhibitor GSK2118436
    • GSK-2118436
    • GSK-2118436A
    • GSK2118436
  • Drug: Dabrafenib Mesylate
    Given PO
    Other Names:
    • Dabrafenib Methanesulfonate
    • GSK2118436 Methane Sulfonate Salt
    • GSK2118436B
    • Tafinlar
  • Drug: Dasatinib
    Given PO
    Other Names:
    • BMS-354825
    • Dasatinib Hydrate
    • Dasatinib Monohydrate
    • Sprycel
  • Drug: Defactinib
    Given PO
  • Drug: Defactinib Hydrochloride
    Given PO
    Other Names:
    • PF-04554878
    • VS-6063
  • Drug: Erdafitinib
    Given PO
    Other Names:
    • Balversa
    • JNJ-42756493
  • Drug: FGFR Inhibitor AZD4547
    Given PO
    Other Name: AZD4547
  • Drug: Ipatasertib
    Given PO
    Other Names:
    • GDC-0068
    • RG-7440
  • Other: Laboratory Biomarker Analysis
    Undergo molecular analysis
  • Drug: Larotrectinib
    Given PO
    Other Names:
    • ARRY 470
    • LOXO 101
    • LOXO-101
  • Drug: Larotrectinib Sulfate
    Given PO
    Other Names:
    • ARRY 470 Sulfate
    • LOXO 101 Sulfate
    • LOXO-101 Sulfate
    • Vitrakvi
  • Biological: Nivolumab
    Given IV
    Other Names:
    • BMS-936558
    • CMAB819
    • MDX-1106
    • NIVO
    • Nivolumab Biosimilar CMAB819
    • ONO-4538
    • Opdivo
  • Drug: Osimertinib
    Given PO
    Other Names:
    • AZD-9291
    • AZD9291
    • Mereletinib
    • Tagrisso
  • Drug: Palbociclib
    Given PO
    Other Names:
    • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
    • Ibrance
    • PD 0332991
    • PD 332991
    • PD 991
    • PD-0332991
  • Biological: Pertuzumab
    Given IV
    Other Names:
    • 2C4
    • 2C4 Antibody
    • HS627
    • MoAb 2C4
    • Monoclonal Antibody 2C4
    • Omnitarg
    • Perjeta
    • Pertuzumab Biosimilar HS627
    • rhuMAb2C4
    • RO4368451
  • Drug: PI3K-beta Inhibitor GSK2636771
    Given PO
    Other Name: GSK2636771
  • Biological: Relatlimab
    Given IV
    Other Names:
    • BMS-986016
    • BMS986016
    • Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer
  • Drug: Sapanisertib
    Given PO
    Other Names:
    • INK-128
    • INK128
    • MLN-0128
    • MLN0128
    • TAK-228
  • Drug: Sunitinib Malate
    Given PO
    Other Names:
    • SU011248
    • SU11248
    • sunitinib
    • Sutent
  • Drug: Taselisib
    Given PO
    Other Names:
    • GDC-0032
    • RO5537381
  • Drug: Trametinib
    Given PO
    Other Names:
    • GSK1120212
    • JTP-74057
    • MEK Inhibitor GSK1120212
  • Biological: Trastuzumab
    Given IV
    Other Names:
    • ABP 980
    • ALT02
    • Anti-c-ERB-2
    • Anti-c-erbB2 Monoclonal Antibody
    • Anti-ERB-2
    • Anti-erbB-2
    • Anti-erbB2 Monoclonal Antibody
    • Anti-HER2/c-erbB2 Monoclonal Antibody
    • Anti-p185-HER2
    • c-erb-2 Monoclonal Antibody
    • HER2 Monoclonal Antibody
    • Herceptin
    • Herceptin Biosimilar PF-05280014
    • Herceptin Trastuzumab Biosimilar PF-05280014
    • Herzuma
    • Kanjinti
    • MoAb HER2
    • Monoclonal Antibody c-erb-2
    • Monoclonal Antibody HER2
    • Ogivri
    • Ontruzant
    • PF-05280014
    • rhuMAb HER2
    • RO0452317
    • SB3
    • Trastuzumab Biosimilar ABP 980
    • Trastuzumab Biosimilar ALT02
    • trastuzumab biosimilar EG12014
    • Trastuzumab Biosimilar HLX02
    • Trastuzumab Biosimilar PF-05280014
    • Trastuzumab Biosimilar SB3
    • Trastuzumab Biosimilar SIBP-01
    • Trastuzumab-anns
    • Trastuzumab-dkst
    • Trastuzumab-dttb
    • Trastuzumab-pkrb
    • Trastuzumab-qyyp
    • Trazimera
  • Biological: Trastuzumab Emtansine
    Given IV
    Other Names:
    • Ado Trastuzumab Emtansine
    • ADO-Trastuzumab Emtansine
    • Kadcyla
    • PRO132365
    • RO5304020
    • T-DM1
    • Trastuzumab-DM1
    • Trastuzumab-MCC-DM1
    • Trastuzumab-MCC-DM1 Antibody-Drug Conjugate
    • Trastuzumab-MCC-DM1 Immunoconjugate
  • Drug: Ulixertinib
    Give PO
    Other Names:
    • BVD-523
    • VRT752271
  • Drug: Vismodegib
    Given PO
    Other Names:
    • Erivedge
    • GDC-0449
    • Hedgehog Antagonist GDC-0449
Study Arms  ICMJE
  • Experimental: Subprotocol A (EGFR activating mutation)
    Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Afatinib
    • Drug: Afatinib Dimaleate
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol B (HER2 activating mutation)
    Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Afatinib
    • Drug: Afatinib Dimaleate
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol C1 (MET amplification)
    Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Crizotinib
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol C2 (MET exon 14 deletion/mutation)
    Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Crizotinib
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol E (EGFR T790M or rare activating mutation)
    Patients with EGFR T790M or rare activating mutation receive osimertinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Osimertinib
  • Experimental: Subprotocol F (ALK translocation)
    Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Crizotinib
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol G (ROS1 translocation or inversion)
    Patients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Crizotinib
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol H (BRAF V600E/R/K/D mutation)
    Patients with BRAF V600E/R/K/D mutation receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Drug: Dabrafenib
    • Drug: Dabrafenib Mesylate
    • Other: Laboratory Biomarker Analysis
    • Drug: Trametinib
  • Experimental: Subprotocol I (PIK3CA mutation)
    Patients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Taselisib
  • Experimental: Subprotocol J (HER2 amplification >= 7 copy numbers)
    Patients with HER2 amplification >= 7 copy numbers receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Biological: Pertuzumab
    • Biological: Trastuzumab
    • Biological: Trastuzumab Emtansine
  • Experimental: Subprotocol K1 (FGFR amplification)
    Patients with FGFR amplification receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Drug: Erdafitinib
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol K2 (FGFR mutation or fusion)
    Patients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Drug: Erdafitinib
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol L (mTOR mutation)
    Patients with mTOR mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Sapanisertib
  • Experimental: Subprotocol M (TSC1 or TSC2 mutation)
    Patients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Sapanisertib
  • Experimental: Subprotocol N (PTEN mutation or deletion and PTEN expression)
    Patients with PTEN mutation or deletion and PTEN expression receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: PI3K-beta Inhibitor GSK2636771
  • Experimental: Subprotocol P (PTEN loss)
    Patients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: PI3K-beta Inhibitor GSK2636771
  • Experimental: Subprotocol Q (HER2 amplification)
    Patients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Biological: Trastuzumab
    • Biological: Trastuzumab Emtansine
  • Experimental: Subprotocol R (BRAF fusion or BRAF non-V600 mutation)
    Patients with BRAF fusion or BRAF non-V600 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Trametinib
  • Experimental: Subprotocol S1 (NF1 mutation)
    Patients with NF1 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Trametinib
  • Experimental: Subprotocol S2 (GNAQ or GNA11 mutation)
    Patients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Trametinib
  • Experimental: Subprotocol T (SMO or PTCH1 mutation)
    Patients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Vismodegib
  • Experimental: Subprotocol U (NF2 inactivating mutation)
    Patients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Drug: Defactinib
    • Drug: Defactinib Hydrochloride
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
    Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib malate PO QD for 4 weeks. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Sunitinib Malate
  • Experimental: Subprotocol W (FGFR pathway aberrations)
    Patients with FGFR1-3 mutation or translocation receive FGFR Inhibitor AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Drug: FGFR Inhibitor AZD4547
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol X (DDR2 S768R, I638F, or L239R mutation)
    Patients with DDR2 S768R, I638F, or L239R mutation receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Drug: Dasatinib
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Y (Akt mutation)
    Patients with Akt mutation receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Capivasertib
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)
    Patients with NRAS mutation in codon 12, 13, or 61 receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Binimetinib
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)
    Patients with CCND1, 2, or 3 amplification that have tumor Rb expression by IHC receive palbociclib PO QD for 21 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Palbociclib
  • Experimental: Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein)
    Patients with CDK4 or CDK6 amplification and tumor Rb protein receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Palbociclib
  • Experimental: Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)
    Patients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) receive nivolumab IV over 30 minutes on days 1 and 15 for 4 cycles and then on day 1 every 28 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
  • Experimental: Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
    Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Larotrectinib
    • Drug: Larotrectinib Sulfate
  • Experimental: Subprotocol Z1F (PIK3CA mutation)
    Patients with PIK3CA mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Copanlisib
    • Drug: Copanlisib Hydrochloride
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Z1G (PTEN loss)
    Patients with PTEN loss receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Copanlisib
    • Drug: Copanlisib Hydrochloride
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Z1H (PTEN mutation)
    Patients with PTEN mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Copanlisib
    • Drug: Copanlisib Hydrochloride
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)
    Patients with BRCA1 or BRCA2 gene mutation receive adavosertib PO QD for 5 days for 2 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Adavosertib
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Z1K (AKT mutation)
    Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Drug: Ipatasertib
    • Other: Laboratory Biomarker Analysis
  • Experimental: Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation)
    Patients with a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration receive ulixertinib (BVD-523FB) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Drug: Ulixertinib
  • Experimental: Subprotocol Z1M (LAG-3 expression >= 1%)
    Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1.Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Cytology Specimen Collection Procedure
    • Other: Laboratory Biomarker Analysis
    • Biological: Nivolumab
    • Biological: Relatlimab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 23, 2017)		 6452
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2015)		 3000
Estimated Study Completion Date  ICMJE June 30, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)

  • Patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration; patients that are pregnant or breast feeding are excluded; a patient of childbearing potential is anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:

    • Has achieved menarche at some point
    • Has not undergone a hysterectomy or bilateral oophorectomy; or
    • Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse prior to study entry, for the duration of study participation, and for 4 months after completion of study; should a patient or partner of the patient become pregnant or suspect a pregnancy while participating in this study, the treating physician should be informed immediately

  • Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the following criteria:

    • Patients must have progressed following at least one line of standard systemic therapy and there must not be other approval/standard therapy available that has been shown to prolong overall survival (i.e. in a randomized trial against another standard treatment or by comparison to historical controls); patients who cannot receive other standard therapy that has been shown to prolong overall survival due to medical issues will be eligible, if other eligibility criteria are met; if the patient is currently receiving therapy, the clinician must have assessed that the current therapy is no longer benefitting the patient prior to enrolling on MATCH, regardless of whether it is considered standard OR
    • Patients for whose disease no standard treatment exists that has been shown to prolong overall survival
    • NOTE: No other prior malignancy is allowed except for the following:
    • Adequately treated basal cell or squamous cell skin cancer
    • In situ cervical cancer
    • Adequately treated stage I or II cancer from which the patient is currently in complete remission
    • Any other cancer from which the patient has been disease-free for 5 years
  • Patients must have measurable disease

  • Patients must meet the criteria below

    • Tumor tissue for the confirmation of "rare variant" by the MATCH assay is to be submitted, preferably from the same time of collection as that used to determine patient candidacy for treatment arm assignment

      • Registration to Step 0 must occur after stopping prior systemic anti-cancer therapy. There is no specific duration for which patients must be off treatment prior to registration to Step 0, as long as all eligibility criteria are met
      • Patients may have received other non-targeted, immunotherapy or targeted treatment between the prior genetic testing at the outside lab and registration to Step 0. The decision to stop such treatment in favor of participation in MATCH, if no further clinical benefit is expected, is per the treating physician's discretion. Documentation of a lack of response to the prior treatment is not required in these cases
      • Patients with an applicable "rare variant" must be able to meet the eligibility criteria for the appropriate subprotocols within 4 weeks following notification of treatment assignment

      • Patient meets one of the following criteria:

        • Patient is a candidate for Z1M based on local CLIA assessment of MMRd by immunohistochemistry (IHC) or MSI status by polymerase chain reaction (PCR), adequate tumor tissue is available for submission for mandatory central screening IHC and the patient will be able to meet the eligibility criteria for Z1M within 4 weeks following notification of treatment assignment OR
        • The sites have received results from one of the designated outside laboratories indicating a "rare variant" that is an actionable Mutation of Interest (aMOI) for specific select subprotocols
    • NOTE: There is no particular window of time after receiving the sequencing report notification of potential eligibility from an outside lab in which the patient must be registered to Step 0, but treatment slots will be assigned on a first come, first serve basis to those who do register to Step 0, and are not held for those notified of potential eligibility who do not register to Step 0
    • NOTE: Treatment assignment (and the start of the associated deadline for Step 1 registration) may occur shortly after Step 0 registration. Note that certain "rare variant" arms require submission of archival tissue for central IHC testing to determine treatment assignment. For those arms, adequate tissue for the central IHC is required to be available for submission
    • NOTE: Other potential aMOIs that would be eligibility criteria for "NON RARE" arms, as determined by the designated laboratories, are not applicable for this process in MATCH
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1 and a life expectancy of at least 3 months
  • Patients must be able to swallow tablets or capsules; a patient with any gastrointestinal disease that would impair ability to swallow, retain, or absorb drug is not eligible

  • Patients who are human immunodeficiency virus (HIV)-positive are eligible if:

    • CD4+ cell count greater or equal to 250 cells/mm^3
    • If patient is on antiretroviral therapy, there must be minimal interactions or overlapping toxicity of the antiretroviral therapy with the experimental cancer treatment; for experimental cancer therapeutics with CYP3A/4 interactions, protease inhibitor therapy is disallowed; suggested regimens to replace protease inhibitor therapy include dolutegravir given with tenofovir/emtricitabine; raltegravir given with tenofovir and emtricitabine; once daily combinations that use pharmacologic boosters may not be used
    • No history of non-malignancy acquired immune deficiency syndrome (AIDS)-defining conditions other than historical low CD4+ cell counts
    • Probable long-term survival with HIV if cancer were not present

  • Any prior therapy, radiotherapy (except palliative radiation therapy of 30 gray [Gy] or less), or major surgery must have been completed >= 4 weeks prior to start of treatment; all adverse events due to prior therapy have resolved to a grade 1 or better (except alopecia and lymphopenia) by start of treatment; palliative radiation therapy must have been completed at least 2 weeks prior to start of treatment; the radiotherapy must not be to a lesion that is included as measurable disease

    • NOTE: Prostate cancer patients may continue their luteinizing hormone-releasing hormone (LHRH) agonist
    • NOTE: For patients entering the study via the original screening process, patients may receive non-protocol treatment after biopsy (if clinically indicated) until they receive notification of results; however, lack of response must be documented prior to registration to Step 1; new non-protocol treatment will NOT be permitted as intervening therapy after registration to Step 0; the only intervening treatment permitted is prior therapy that the patient already received prior to Step 0 registration; the decision to stop the intervening non-protocol treatment will be left up to the treating physician if patient has an aMOI; however, patients will need to be off such therapy for at least 4 weeks before receiving any MATCH protocol treatment
    • NOTE: For patients entering the study via a designated outside laboratory, no intervening systemic non-protocol treatment is permitted after Step 0 registration; all other eligibility requirements still apply to these patients, including the washouts for prior therapy noted above in this section, the time restrictions outlined, and the eligibility criteria for the intended subprotocol
  • Patients with brain metastases or primary brain tumors must have completed treatment, surgery or radiation therapy >= 4 weeks prior to start of treatment

  • Patients must have discontinued steroids >= 1 week prior to registration to Step 0 and remain off steroids thereafter, except as permitted; patients with glioblastoma (GBM) must have been on stable dose of steroids, or be off steroids, for one week prior to registration to treatment (Step 1, 3, 5, 7)

    • NOTE: The following steroids are permitted (low dose steroid use is defined as prednisone 10 mg daily or less, or bioequivalent dose of other corticosteroid):

      • Temporary steroid use: e.g. for computed tomography (CT) imaging in setting of contrast allergy
      • Low dose steroid use for appetite
      • Chronic inhaled steroid use
      • Steroid injections for joint disease
      • Stable dose of replacement steroid for adrenal insufficiency or low doses for non-malignant disease
      • Topical steroid
      • Steroids required to manage toxicity related to study treatment, as described in the subprotocols

      • Steroids required as pre- or post-chemotherapy medication for acceptable intervening chemotherapy

        • NOTE: Steroids must be completed alongside last dose of chemotherapy
  • Leukocytes >= 3,000/mcL (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
  • Absolute neutrophil count (ANC) >= 1,500/mcL (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
  • Platelets >= 100,000/mcL (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
  • NOTE: Patients with documented bone marrow involvement by lymphoma are not required to meet the above hematologic parameters, but must have a platelet count of at least 75,000/mcL and neutrophil count of at least 1,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless documented Gilbert's syndrome, for which bilirubin =< 3 x institutional ULN is permitted) (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (up to 5 times ULN in presence of liver metastases) (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)

  • Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above institutional ULN

    • As defined by the Cockcroft-Gault equation (within 2 weeks prior to screening step registration and within 4 weeks prior to treatment step registration)

  • Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to screening step and must meet the following cardiac criteria:

    • Resting corrected QT interval (QTc) =< 480 msec

      • NOTE: If the first recorded QTc exceeds 480 msec, two additional, consecutive ECGs are required and must result in a mean resting QTc =< 480 msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks between the ECGs

    • The following only need to be assessed if the mean QTc > 480 msec

      • Check potassium and magnesium serum levels
      • Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG to confirm exclusion of patient due to QTc
      • For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual read of QTc is required
      • For patients with baseline HR < 60 or > 100 bpm, manual read of QT by trained personnel is required, with Fridericia correction applied to determine QTc
      • Patient must not have hypokalemia (value < institutional lower limit of normal)

    • No factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval

      • NOTE: Patient must be taken off prohibited medication prior to registration to the screening step (Step 0, 2, 4, 6) and remain off these medications thereafter, unless permitted on a subprotocol for the management of treatment related toxicity; patient must be off the drug for at least 5 half-lives prior to registration to the treatment step (Step 1, 3, 5, 7); the medication half-life can be found in the package insert for Food and Drug Administration (FDA) approved drugs
  • ELIGIBILITY CRITERIA FOR FIRST TREATMENT (STEP 1)
  • NOTE: For patients entering step 0 with assay results from outside laboratories, no systemic treatment is allowed after step 0 registration

  • As MATCH is designed to add additional subprotocols, implement limited expansions of accrual for certain subprotocols, and/or amend existing arm-specific eligibility criteria, some patients entering under the original screening method may be eligible to have their results rerun in MATCHbox, even if they did not match to a treatment initially or did not receive a treatment assignment due to a lack of available assignment slots; patients whose sequence results will be rerun through MATCHbox must also meet the following criteria:

    • Samples must have been collected within 5 months of the activation of the addendum, as there is an additional month needed to get the patients on trial
    • Patient has not had treatment within the 5 months that resulted in a PR or better after the performance of the screening assessment
    • Patient must meet eligibility criteria, including performance status 1 or better and life expectancy of at least 3 months

    • Patients must meet the eligibility requirements with the following exceptions:

      • Patients may have received other non-targeted, immunotherapy or targeted treatment, which could be stopped in favor of returning to MATCH, if no response to the interim treatment has occurred and no further benefit is expected from this interim treatment, per the treating physician's discretion; documentation of a lack of response to the interim treatment is not required in these cases; however, the following restrictions apply:

        • Enrollment onto another investigational therapeutic study is not permitted
        • Patient cannot be responding to interim treatment, since the benefit of the MATCH treatment is unknown and may deprive patient of an effective treatment if it were given when a patient is responding to another treatment
    • NOTE: Patients meeting these criteria will NOT be biopsied at this time point; instead, their step 0 results will be re-interrogated to determine if another treatment is available
  • ELIGIBILITY CRITERIA FOR SECOND SCREENING (STEP 2)
  • Patient's disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Guam,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02465060
Other Study ID Numbers  ICMJE NCI-2015-00054
NCI-2015-00054 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EAY131
EAY131 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EAY131 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
U24CA196172 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Keith T Flaherty ECOG-ACRIN Cancer Research Group
PRS Account National Cancer Institute (NCI)
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP