Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
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 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:
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:
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
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.
Subjects with known active CNS metastasis
Primary purpose
Allocation
Interventional model
Masking
117 participants in 3 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal