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Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer

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ClinicalTrials.gov Identifier: NCT03432741
Recruitment Status : Suspended (To assess costs associated with the study)
First Posted : February 14, 2018
Last Update Posted : May 30, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Brief Summary:
This pilot phase I trial studies the side effects of direct tumor microinjection and fludeoxyglucose F-18 positron emission tomography (FDG-PET) in testing drug sensitivity in patients with non-Hodgkin lymphoma, Hodgkin lymphoma, or stage IV breast cancer that has returned after a period of improvement or does not respond to treatment. Injecting tiny amounts of anti-cancer drugs directly into tumors on the skin or in lymph nodes and diagnostic procedures, such as FDG-PET, may help to show which drugs work better in treating patients with non-Hodgkin lymphoma, Hodgkin lymphoma, or breast cancer.

Condition or disease Intervention/treatment Phase
Breast Adenocarcinoma Recurrent Breast Carcinoma Recurrent Hodgkin Lymphoma Recurrent Mycosis Fungoides Recurrent Non-Hodgkin Lymphoma Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Refractory Hodgkin Lymphoma Refractory Mycosis Fungoides Refractory Nodal Marginal Zone Lymphoma Refractory Non-Hodgkin Lymphoma Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma Stage IV Breast Cancer AJCC v6 and v7 Drug: Belinostat Drug: Carfilzomib Biological: Daratumumab Drug: Fludeoxyglucose F-18 Drug: Gemcitabine Hydrochloride Other: Laboratory Biomarker Analysis Biological: Nivolumab Biological: Obinutuzumab Biological: Pembrolizumab Procedure: Positron Emission Tomography Biological: Rituximab Drug: Romidepsin Other: Saline Biological: Trastuzumab Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety of in vivo in host drug sensitivity testing in patients with breast cancer and patients with lymphoma (nodal, extranodal or cutaneous lesions).

SECONDARY OBJECTIVES:

I. To assess the feasibility of in vivo in host drug sensitivity testing in this patient population.

II. To identify targeted therapies with potential activity in relapsed lymphoma and metastatic breast cancer.

III. To evaluate the adverse event profile within each patient population.

TERTIARY OBJECTIVES:

I. To assess for apoptosis in response to intratumoral injection using known biomarkers (e.g., by morphology, Ki-67, caspace-3 assay as a marker of early apoptosis).

II. To evaluate intratumoral biomarkers, intratumoral cell populations, and distribution, identify potential biomarkers that correlate with response to therapy based on individual therapies.

OUTLINE:

Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal disease undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging FDG-PET, photography, and biopsy.

After completion of study treatment, patients are followed up at 3 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Safety and Feasibility Study of an In Vivo Sensitivity Screen Using a Direct Tumor Microinjection Technique and FDG-PET
Actual Study Start Date : March 27, 2018
Estimated Primary Completion Date : July 1, 2019
Estimated Study Completion Date : July 1, 2019


Arm Intervention/treatment
Experimental: Treatment (FDG-PET, direct tumor microinjection)
Patients undergo FDG-PET and receive saline intralesionally on day 1. Patients also receive up to five additional injections of gemcitabine hydrochloride, romidepsin, belinostat, carfilzomib, nivolumab, trastuzumab, daratumumab, obinutuzumab, pembrolizumab, or rituximab intralesionally per investigator on day 1. Beginning 5 days later, patients with nodal disease undergo restaging FDG-PET and biopsy (if clinically feasible). Within 3-7 days, patients with cutaneous disease undergo restaging FDG-PET, photography, and biopsy.
Drug: Belinostat
Given intralesionally
Other Names:
  • Beleodaq
  • PXD 101
  • PXD101

Drug: Carfilzomib
Given intralesionally
Other Names:
  • Kyprolis
  • PR-171

Biological: Daratumumab
Given intralesionally
Other Names:
  • Anti-CD38 Monoclonal Antibody
  • Darzalex
  • HuMax-CD38
  • JNJ-54767414

Drug: Fludeoxyglucose F-18
Undergo FDG-PET
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18

Drug: Gemcitabine Hydrochloride
Given intralesionally
Other Names:
  • dFdCyd
  • Difluorodeoxycytidine Hydrochloride
  • Gemzar
  • LY-188011
  • LY188011

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Nivolumab
Given intralesionally
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Biological: Obinutuzumab
Given intralesionally
Other Names:
  • Anti-CD20 Monoclonal Antibody R7159
  • GA-101
  • GA101
  • Gazyva
  • huMAB(CD20)
  • R7159
  • RO 5072759

Biological: Pembrolizumab
Given intralesionally
Other Names:
  • Keytruda
  • Lambrolizumab
  • MK-3475
  • SCH 900475

Procedure: Positron Emission Tomography
Undergo FDG-PET
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging

Biological: Rituximab
Given intralesionally
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Drug: Romidepsin
Given intralesionally
Other Names:
  • Antibiotic FR 901228
  • Depsipeptide
  • FK228
  • FR901228
  • Istodax
  • N-[(3S,4E)-3-Hydroxy-7-mercapto-1-oxo-4-heptenyl]-D-valyl-D-cysteinyl-(2Z)-2-amino-2-butenoyl-L-valine, (4->1) Lactone, Cyclic

Other: Saline
Given intralesionally
Other Name: Sodium Chloride 0.9%

Biological: Trastuzumab
Given intralesionally
Other Names:
  • ABP 980
  • 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
  • MoAb HER2
  • Monoclonal Antibody c-erb-2
  • Monoclonal Antibody HER2
  • Ogivri
  • PF-05280014
  • rhuMAb HER2
  • RO0452317
  • Trastuzumab Biosimilar ABP 980
  • Trastuzumab Biosimilar PF-05280014
  • Trastuzumab-dkst




Primary Outcome Measures :
  1. Incidence of drug sensitivity as measured by injection site skin reaction [ Time Frame: Up to 3 months ]
    Skin reactions will be assessed using the Cancer Therapy Evaluation Program (CTEP) active version of the Common Terminology Criteria for Adverse Events (CTCAE) and will consist of any grade 3 or higher treatment-related pain, skin or subcutaneous tissue disorders. Incidence rates of skin reactions will be estimated by the number of patients with reactions divided by the total number of evaluable patients per disease type. Exact binomial 95% confidence intervals for the true incidence rate will be calculated.


Secondary Outcome Measures :
  1. Cutaneous response rate based upon the modified Severity Weighted Assessment Tool score [ Time Frame: Up to 7 days post injection ]
    Will be estimated by the number of injection sites with responses divided by the total number of injected sites. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

  2. Feasibility defined as at least 70% of the enrolled patients complete the injection and response evaluation [ Time Frame: Up to 3 months ]
    The feasibility rate will be estimated by the number of patients completed divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true feasibility rate will be calculated.

  3. Incidence of adverse events [ Time Frame: Up to 3 months ]
    Will be evaluated using the CTEP active version of the CTCAE. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

  4. Nodal disease response rate [ Time Frame: Up to 5 days post injection ]
    Defined as a decrease in standardized uptake value (SUV) uptake by 25% at site of injection. Will be estimated by the number of injection sites with responses divided by the total number of injected sites. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.


Other Outcome Measures:
  1. Apoptosis in response to intratumoral injection [ Time Frame: Up to 3 months ]
    Will assess using morphology (evidence of necrosis), measurement by immunohistochemistry of Ki67 (a marker of cell proliferation) and cleaved Caspace-3.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven within the last 6 months of relapsed or refractory

    • Non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) nodal or extranodal OR
    • Cutaneous T-cell lymphoma (CTCL) including mycosis fungoides (MF), as well as transformed MF OR
    • Breast adenocarcinoma with nodal or cutaneous metastases (stage 4)

      • NOTE: Patients must be refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition
      • NOTE: The patient must not be a candidate for any curative therapy or any known life-prolonging therapy
  • Presence of lesions that are amenable for injections as determined by interventional radiology

    • NOTE: Nodal or extranodal sites must be palpable and easily accessible; sites such as mediastinum, retroperitoneum, within solid organs, spinal sites, central nervous system (CNS) sites, etc., are NOT allowed
  • Measurable disease:

    • For nodal or extranodal disease (lymphoma or breast): must have at least 2 lesions that are >= 20 mm (2.0 cm) in the longest diameter by physical exam and/or on cross-sectional imaging and measurable in two perpendicular dimensions per computed tomography PET-computed tomography (CT), that are amenable to intralesional injections as determined by interventional radiology (including tumors that can be safely accessed using imaging guidance and treated with minimal risk to adjacent structures)
    • For cutaneous lesions (lymphoma or breast): at least two visible, non-infected skin lesions that are greater than 1 cm and are amenable to intralesional injection
  • Candidate for further therapy and able to wait 7 days prior to start of next systemic therapy
  • Absolute neutrophil count (ANC) >= 1000/mm^3 obtained =< 14 days prior to registration
  • Platelet count >= 50,000/mm^3 obtained =< 14 days prior to registration
  • International normalized ratio (INR)/prothrombin time (PT) =< 1.5 obtained =< 14 days prior to registration
  • Negative serum or urine pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up
  • Willing to provide tissue samples for correlative research purposes

Exclusion Criteria:

  • Any of the following:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Systemic corticosteroids between pre-PET and post-PET evaluation and biopsy
  • Prohibited treatments and or therapies

    • Autologous stem cell transplant (ASCT) =< 12 weeks prior to registration
    • Prior chemotherapy =< 2 weeks prior to registration
    • Prior treatment with nitrosureas =< 4 weeks prior to registration
    • Therapeutic anticancer antibodies =< 2 weeks prior to registration
    • Radio- or toxin immunoconjugates =< 4 weeks prior to registration
    • Radiation therapy to the injected area =< 2 weeks prior to registration
    • Major surgery =< 2 weeks prior to registration
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Requires anticoagulation that cannot be discontinued prior to biopsy

    • Note: Exception if able to hold antiplatelet agents 7 days prior to the injections and biopsy
    • NOTE: Low molecular weight heparin (LMWH) will be allowed for bridging if on warfarin
    • NOTE: Heparin for line patency without detectable lab abnormalities for coagulation will be allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03432741


Locations
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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Grzegorz Nowakowski Mayo Clinic

Additional Information:
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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT03432741     History of Changes
Other Study ID Numbers: MC1689
NCI-2018-00149 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1689 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: February 14, 2018    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lymphoma
Breast Neoplasms
Adenocarcinoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, B-Cell, Marginal Zone
Mycoses
Mycosis Fungoides
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Breast Diseases
Skin Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Lymphoma, B-Cell
Gemcitabine
Belinostat
Rituximab
Pembrolizumab
Nivolumab
Trastuzumab
Obinutuzumab
Daratumumab