Clinical Trial - NCT03043313

Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

Recruiting

Sponsor: Seattle Genetics, Inc.

Collaborators: National Cancer Institute (NCI), Academic and Community Cancer Research United

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03043313

Protocol Info

Short Description: Tucatinib + Trastuzumab in Colorectal Cancer
Long Description: MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined with Trastuzumab in Patients with HER2+ Metastatic Colorectal Cancer
MGH Status: Open
Sponsor: Seattle Genetics
Disease Program: GI

Next Steps


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Purpose

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.
Condition Title Intervention Phase
Metastatic Colorectal Adenocarcinoma Trastuzumab Tucatinib Phase 2
Study Type Interventional
Official Title MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer

Primary Outcome Measures

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] [Designated as safety issue: ]


Secondary Outcome Measures

ORR at 12 weeks of treatment per RECIST 1.1 according to BICR assessment [Time Frame: Up to 12 weeks] [Designated as safety issue: ]

Duration of response (DOR) per RECIST 1.1 according to BICR assessment [Time Frame: Up to approximately 4 years] [Designated as safety issue: ]

Progression-free survival (PFS) per RECIST 1.1 according to BICR assessment for pooled Cohorts A+B [Time Frame: Up to approximately 4 years] [Designated as safety issue: ]

Overall survival (OS) in pooled Cohorts A+B [Time Frame: Up to approximately 4 years] [Designated as safety issue: ]

Incidence of adverse events (AEs) [Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject] [Designated as safety issue: ]

Incidence of dose modifications [Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject] [Designated as safety issue: ]

Incidence of laboratory abnormalities [Time Frame: Through 30 days following last dose; up to approximately 9 months overall per subject] [Designated as safety issue: ]

Estimated Enrollment: 110
Study Start Date: June 2017
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: August 2021
Arms Assigned Interventions

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.
Drug:Tucatinib
Given orally

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.

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.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03043313

Locations

  • United States, Arizona
    • Mayo Clinic Arizona Phoenix, Arizona, United States, 85054
  • United States, California
    • Keck Medical Center / University of Southern California Los Angeles, California, United States, 90033
    • Saint Joseph Heritage Medical Group Santa Rosa, California, United States, 95403
  • United States, Florida
    • Florida Cancer Specialists - South Region Fort Myers, Florida, United States, 33901
    • Florida Cancer Specialists - North Region Saint Petersburg, Florida, United States, 33705
  • United States, Georgia
    • Winship Cancer Institute / Emory University School of Medicine Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • University of Chicago Medical Center Chicago, Illinois, United States, 60637-1470
  • United States, Kansas
    • University of Kansas Cancer Center Westwood, Kansas, United States, 66205
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Minnesota
    • Mayo Clinic Rochester Rochester, Minnesota, United States, 55905
  • United States, New York
    • Roswell Park Cancer Institute Buffalo, New York, United States, 14203
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, North Carolina
    • Duke University Medical Center Durham, North Carolina, United States, 27710
  • United States, Ohio
    • Case Western Reserve University / University Hospitals Cleveland Medical Center Cleveland, Ohio, United States, 44106
  • United States, Oregon
    • Oregon Health and Science University Portland, Oregon, United States, 97239-3098
  • United States, Pennsylvania
    • Allegheny General Hospital Pittsburgh, Pennsylvania, United States, 15212
  • United States, Tennessee
    • Tennessee Oncology-Nashville/Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203
    • Vanderbilt University Medical Center Nashville, Tennessee, United States, 37204
  • United States, Texas
    • Joe Arrington Cancer Research and Treatment Center Lubbock, Texas, United States, 79410
  • United States, Utah
    • Huntsman Cancer Institute/University of Utah Salt Lake City, Utah, United States, 84112
  • United States, Washington
    • Seattle Cancer Care Alliance / University of Washington Seattle, Washington, United States, 98109-1023
  • United States, Wisconsin
    • Aurora Research Institute Cancer Center Milwaukee, Wisconsin, United States, 53215

Sponsors and Collaborators

Seattle Genetics, Inc.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03043313
Other Study ID Numbers: NCI-2017-01107
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Seattle Genetics, Inc.:

HER2

ERBB2

Colorectal cancer

Additional relevant MeSH terms:

Colorectal Neoplasms

Trastuzumab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on September 03, 2020