Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer

Completed · Phase 2

Conditions studied: Metastatic Colorectal Adenocarcinoma

In brief

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.

Key facts

Study ID

NCT03043313

Run by

Seagen Inc.

People needed

117

Starts

2017-06-23

Expected to finish

2023-11-02

Last updated by the study team

2024-11-26

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 recently available 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 or International Organization for Standardization (ISO)-accredited laboratory, meeting at least one of the following criteria:
• HER2+ overexpression (3+ immunohistochemistry [IHC]) by an FDA-approved or Conformité Européene (CE)-marked HER2 ICH test
• HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization [CISH]))
• HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited 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

You may not qualify if…

• 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
• 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 strong 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.
• Exceptions are malignancies with a negligible risk of metastasis or death
• Subjects with known active CNS metastasis
• 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

Where it is running

• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
• Mayo Clinic Arizona — Phoenix, Arizona, United States
• Pacific Shores Medical Group — Long Beach, California, United States
• Keck Medical Center / University of Southern California — Los Angeles, California, United States
• Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute — Los Angeles, California, United States
• Stanford University School of Medicine — Palo Alto, California, United States
• Saint Joseph Heritage Medical Group — Santa Rosa, California, United States
• Rocky Mountain Cancer Centers - Aurora — Aurora, Colorado, United States
• Lombardi Cancer Center / Georgetown University Medical Center — Washington D.C., District of Columbia, United States
• Florida Cancer Specialists - South Region — Fort Myers, Florida, United States
• Florida Cancer Specialists - North Region — St. Petersburg, Florida, United States
• Winship Cancer Institute / Emory University School of Medicine — Atlanta, Georgia, United States
• University of Chicago Medical Center — Chicago, Illinois, United States
• Indiana University Simon Cancer Center — Indianapolis, Indiana, United States
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States
• University of Kansas Cancer Center — Westwood, Kansas, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Karmanos Cancer Institute / Wayne State University — Detroit, Michigan, United States
• Mayo Clinic Rochester — Rochester, Minnesota, United States
• Comprehensive Cancer Centers of Nevada — Las Vegas, Nevada, United States
• Roswell Park Cancer Institute — Buffalo, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Duke University Medical Center — Durham, North Carolina, United States
• University of Alabama at Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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