Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT03043313|
Recruitment Status : Active, not recruiting
First Posted : February 6, 2017
Last Update Posted : June 8, 2022
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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 or disease||Intervention/treatment||Phase|
|Metastatic Colorectal Adenocarcinoma||Drug: Trastuzumab Drug: Tucatinib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||117 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer|
|Actual Study Start Date :||June 23, 2017|
|Actual Primary Completion Date :||March 28, 2022|
|Estimated Study Completion Date :||April 30, 2023|
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.
Given intravenously (into the vein; IV)
Other Name: Herceptin
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.
Given intravenously (into the vein; IV)
Other Name: Herceptin
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.
- 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).
- ORR at 12 weeks of treatment per RECIST 1.1 according to BICR assessment [ Time Frame: Up to 12 weeks ]ORR by Week 12 is defined as the proportion of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.
- Duration of response (DOR) per RECIST 1.1 according to BICR assessment [ Time Frame: Up to approximately 4 years ]DOR is defined as the time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of progressive disease or to death due to any cause, whichever comes first.
- 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 ]
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.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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
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): NCT03043313
|Study Chair:||John H Strickler||Academic and Community Cancer Research United|
|Study Director:||Michael Stecher, MD||Seagen Inc.|
|Responsible Party:||Seagen Inc.|
|Other Study ID Numbers:||
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 )
|First Posted:||February 6, 2017 Key Record Dates|
|Last Update Posted:||June 8, 2022|
|Last Verified:||June 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Antineoplastic Agents, Immunological
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action