MOUNTAINEER-03: A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer
Study Details
Study Description
Brief Summary
This study is being done to find out if tucatinib with other cancer drugs works better than standard of care to treat participants with HER2 positive colorectal cancer. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.
Participants in this study have colorectal cancer that has spread through the body (metastatic) and/or cannot be removed with surgery (unresectable).
Participants will be assigned randomly to a group to the tucatinib or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either:
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mFOLFOX6 alone,
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mFOLFOX6 with bevacizumab, or
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mFOLFOX6 with cetuximab These are drugs that are used to treat this type of cancer.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Tucatinib Arm Tucatinib + trastuzumab + mFOLFOX6 |
Drug: tucatinib
300mg given by mouth (orally) twice daily
Other Names:
Drug: trastuzumab
8mg/kg loading dose will be given into the vein (IV; intravenously) on Cycle 1 day 1, followed by 6mg/kg given by IV every 3 weeks thereafter.
Other Names:
Drug: oxaliplatin
85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.
Drug: leucovorin
400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.
Drug: levoleucovorin
200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.
Drug: fluorouracil
400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.
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Active Comparator: Standard of Care Arm mFOLFOX6 + (bevacizumab OR cetuximab). Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab |
Drug: bevacizumab
5mg/kg given by IV every 2 weeks
Other Names:
Drug: cetuximab
400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly
Other Names:
Drug: oxaliplatin
85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.
Drug: leucovorin
400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.
Drug: levoleucovorin
200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.
Drug: fluorouracil
400mg/m2 given by IV bolus then 2400mg/m2 given by continuous IV infusion (over 46-48 hours) every 2 weeks. Component of mFOLFOX6.
|
Outcome Measures
Primary Outcome Measures
- Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR) [Up to approximately 3 years]
The time from the date of randomization to the BICR assessment of disease progression according to RECIST v1.1 or death from any cause
Secondary Outcome Measures
- Overall survival (OS) [Up to approximately 6 years]
The time from randomization to death from any cause
- Confirmed objective response rate (cORR) per RECIST v1.1 by BICR [Up to approximately 3 years]
The proportion of subjects with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by BICR
- PFS per RECIST v1.1 by investigator assessment [Up to approximately 3 years]
The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause
- cORR per RECIST v1.1 by investigator assessment [Up to approximately 3 years]
The proportion of subjects with confirmed CR or PR according to RECIST v1.1, as assessed by investigators
- Duration of response (DOR) per RECIST v1.1 by BICR [Up to approximately 3 years]
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause
- DOR per RECIST v1.1 by investigator assessment [Up to approximately 3 years]
The time from first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of disease progression per RECIST v1.1 or death from any cause
- Time to second progression or death (PFS2) [Up to approximately 3 years]
The time from randomization to disease progression on the next-line of therapy, or death from any cause
- Incidence of adverse events (AEs) [Through 30 days after the last study treatment; approximately 1 year]
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
- Incidence of dose alterations [Through 30 days after the last study treatment; approximately 1 year]
- Trough concentration (Ctrough) [Approximately 4 months]
PK parameter
- Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30) score [Through 30-37 days after the last study treatment; approximately 1 year]
The EORTC questionnaires measure aspects of health-related quality of life (HRQoL).
- Time to meaningful change in EORTC QLQ30 score [Through 30-37 days after the last study treatment; approximately 1 year]
The time from baseline to the first onset of a ≥10-point changes in global health status/quality of life (QoL)
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is metastatic and/or unresectable
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Able to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides) obtained prior to treatment initiation to a central laboratory
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If archival tissue is not available, a newly-obtained baseline biopsy of an accessible tumor lesion is required within 35 days prior to start of study treatment
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HER2+ disease as determined by a tissue based assay performed at a central laboratory.
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Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing
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Radiographically measurable disease per RECIST v1.1 with:
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At least one site of disease that is measurable and that has not been previously irradiated, or
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If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
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Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
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CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following:
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No evidence of brain metastases
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Previously treated brain metastases which are asymptomatic
Exclusion Criteria:
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Prior systemic anticancer therapy for colorectal cancer (CRC) in the metastatic setting
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May have received chemotherapy for CRC in the adjuvant setting if it was completed >6 months prior to enrollment
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Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery)
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Previous treatment with anti-HER2 therapy
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Ongoing Grade 3 or higher neuropathy
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GI perforation within 12 months of enrollment
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Pacific Cancer Medical Center | Anaheim | California | United States | 92801 |
2 | Los Angeles Cancer Network | Los Angeles | California | United States | 90017 |
3 | Kaiser Permanente Southern California | Los Angeles | California | United States | 90027 |
4 | Saint Joseph Heritage Medical Group | Santa Rosa | California | United States | 95403 |
5 | HealthPartners Institute | Saint Louis Park | Minnesota | United States | 55416 |
6 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
7 | Gabrail Cancer Center Research, LLC | Canton | Ohio | United States | 44718 |
8 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
9 | US Oncology Investigational Products Center (IPC) | Irving | Texas | United States | 75063 |
10 | Texas Oncology - McKinney | McKinney | Texas | United States | 75071 |
11 | Texas Oncology - Paris | Paris | Texas | United States | 75460 |
12 | US Oncology Central Regulatory | The Woodlands | Texas | United States | 77380 |
13 | Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer Care | Roanoke | Virginia | United States | 24014 |
14 | Northwest Cancer Specialists, P.C. | Vancouver | Washington | United States | 98684 |
Sponsors and Collaborators
- Seagen Inc.
- Merck Sharp & Dohme LLC
Investigators
- Study Director: James Ward, MD, Seagen Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SGNTUC-029