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Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

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ClinicalTrials.gov Identifier: NCT03043313
Recruitment Status : Recruiting
First Posted : February 6, 2017
Last Update Posted : August 4, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Information provided by (Responsible Party):
Seattle Genetics, Inc.

Tracking Information
First Submitted Date  ICMJE January 31, 2017
First Posted Date  ICMJE February 6, 2017
Last Update Posted Date August 4, 2020
Actual Study Start Date  ICMJE June 23, 2017
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2019)
Confirmed objective response rate (cORR) per RECIST 1.1 per blinded independent central review (BICR) in pooled Cohorts A+B [ Time Frame: Up to 8 months ]
cORR is defined as confirmed complete response (CR) or partial response (PR).
Original Primary Outcome Measures  ICMJE
 (submitted: February 2, 2017)
Objective Response Rate (ORR) defined as achieving Complete Response (CR) or Partial Response (PR) [ Time Frame: Through study completion, an average of 7 months ]
ORR is defined as a complete response (CR) or partial response (PR) measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 over the treatment period, with the exception that 4-week confirmatory scans will not be required. The primary hypothesis will be tested in the cohort of eligible patients.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2019)
  • ORR at 12 weeks of treatment per RECIST 1.1 according to BICR assessment [ Time Frame: Up to 12 weeks ]
  • Duration of response (DOR) per RECIST 1.1 according to BICR assessment [ Time Frame: Up to approximately 4 years ]
  • Progression-free survival (PFS) per RECIST 1.1 according to BICR assessment for pooled Cohorts A+B [ Time Frame: Up to approximately 4 years ]
    PFS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to first documentation of tumor progression or to death due to any cause.
  • Overall survival (OS) in pooled Cohorts A+B [ Time Frame: Up to approximately 4 years ]
    OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.
  • Incidence of adverse events (AEs) [ Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject ]
  • Incidence of dose modifications [ Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject ]
  • Incidence of laboratory abnormalities [ Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2017)
  • Clinical Best Response (CBR) [ Time Frame: Up to 3 years ]
    Stable disease (SD) ≥6 months or best response of CR or PR estimated by 95% confidence interval estimates
  • Overall Survival (OS) [ Time Frame: Up to 3 years ]
    Time from registration to time of death
  • Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
    Time from registration to earliest date documentation off disease progression
  • Duration of response [ Time Frame: Up to 3 years ]
    For all eligible patients who have achieved an objective response, duration of response is defined as time from patient's earliest best objective status noted to be either CR or PR to the earliest date progression is documented.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer
Official Title  ICMJE MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer
Brief Summary

This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body.

In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Colorectal Adenocarcinoma
Intervention  ICMJE
  • Drug: Trastuzumab
    Given intravenously (into the vein; IV)
    Other Name: Herceptin
  • Drug: Tucatinib
    Given orally
    Other Names:
    • ARRY-380
    • ONT-380
Study Arms  ICMJE
  • Experimental: Cohort A: Tucatinib + Trastuzumab
    Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
    Interventions:
    • Drug: Trastuzumab
    • Drug: Tucatinib
  • Experimental: Cohort B: Tucatinib + Trastuzumab
    Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
    Interventions:
    • Drug: Trastuzumab
    • Drug: Tucatinib
  • Experimental: Cohort C: Tucatinib Monotherapy
    Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
    Intervention: Drug: Tucatinib
Publications * Not Provided

*   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: November 22, 2019)
110
Original Estimated Enrollment  ICMJE
 (submitted: February 2, 2017)
35
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  • Histologically and/or cytologically documented adenocarcinoma of the colon or rectum that is metastatic and/or unresectable
  • Unless contraindicated, participants must have received and failed regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is MSI-High.
  • Have progression of unresectable or metastatic CRC after the last systemic therapy, or be intolerant of last systemic therapy
  • Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS testing
  • Willing and able to provide the most recent tissue blocks obtained prior to treatment initiation. If archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor
  • Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, meeting at least one of the following criteria:

    • HER2+ overexpression (3+ immunohistochemistry [IHC])by an FDA-approved HER2 ICH test
    • HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH]))
    • HER2 (ERBB2) amplification by CLIA-certified next generation sequencing (NGS) sequencing assay
  • Have radiographically measurable disease assessable by RECIST 1.1, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
  • Life expectancy greater than 3 months
  • Have adequate hematological, hepatic, renal, coagulation, and cardiac function

Exclusion Criteria

  • Previous treatment with anti-HER2 targeting therapy
  • Previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent within 3 weeks of first dose of study treatment
  • Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:

    • Alopecia and neuropathy, which must have resolved to ≤ Grade 2
    • Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the time of occurrence, and must have resolved completely
    • Anemia, which must have resolved to ≤ Grade 2
    • Decreased ANC, which must have resolved to ≤ Grade 2
  • Have clinically significant cardiopulmonary disease
  • Have known myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment
  • Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or anticipation of need for major surgical procedure during the study
  • Serious, non-healing wound, ulcer, or bone fracture
  • Known to be positive for hepatitis B by surface antigen expression
  • Known to have active hepatitis C infection

    o Exception for participants with a documented sustained virologic response of 12 weeks

  • Known to be positive for human immunodeficiency virus (HIV)
  • Subjects who are pregnant, breastfeeding, or planning a pregnancy
  • Inability to swallow pills or any significant gastrointestinal disease which would preclude the adequate oral absorption of medications
  • Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a CYP2C8 or CYP3A4 inducer within 5 days prior to first dose of study treatment
  • History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy.

    o Exceptions are malignancies with a negligible risk of metastasis or death

  • Subjects with known active CNS metastasis o Irradiated or resected lesions are permitted, provided the lesions are fully treated and inactive, subject is asymptomatic, and no steroids have been administered for at least 30 days
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03043313
Other Study ID Numbers  ICMJE SGNTUC-017
NCI-2017-01107 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACCRU-GI-1617 ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Seattle Genetics, Inc.
Study Sponsor  ICMJE Seattle Genetics, Inc.
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Academic and Community Cancer Research United
Investigators  ICMJE
Study Chair: John H Strickler Academic and Community Cancer Research United
Study Director: Michael Stecher, MD Seattle Genetics, Inc.
PRS Account Seattle Genetics, Inc.
Verification Date August 2020

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