Vanderbilt Clinical Trials

A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer

Purpose

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 the tucatinib group or standard of care group. The tucatinib group will get tucatinib, trastuzumab, and mFOLFOX6. The standard of care group will get either: - mFOLFOX6 alone, - mFOLFOX6 with bevacizumab, or - mFOLFOX6 with cetuximab mFOLFOX6 is a combination of multiple drugs. All of the drugs given in this study are used to treat this type of cancer.

Condition

Colorectal Neoplasms

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Histologically and/or cytologically confirmed adenocarcinoma of the colon or rectum which is locally advanced unresectable or metastatic - 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 - 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 - HER2+ disease as determined by a tissue based assay performed at a central laboratory. - Participant has rat sarcoma viral oncogene homolog wild-type (RAS WT) disease as determined by local or central testing. For central RAS analysis, tissue sample must be analyzed within 1 year of biopsy date. - Radiographically measurable disease per RECIST v1.1 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 of 0 or 1 - CNS Inclusion - based on contrast brain magnetic resonance imaging, participants may have any of the following: - No evidence of brain metastases - Previously treated brain metastases which are asymptomatic

Exclusion Criteria

Prior systemic anticancer therapy for colorectal cancer (CRC) in the metastatic setting; note that participants may have received a maximum of 2 doses of mFOLFOX6 in the locally advanced/unresectable or metastatic setting prior to randomization. - Note: May have received chemotherapy for CRC in the adjuvant setting if it was completed >6 months prior to enrollment - Radiation therapy within 14 days prior to enrollment (or within 7 days in the setting of stereotactic radiosurgery) - Previous treatment with anti-HER2 therapy - Ongoing Grade 3 or higher neuropathy - GI perforation within 12 months of enrollment

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Tucatinib Arm	Tucatinib + trastuzumab + mFOLFOX6	Drug: tucatinib 300mg given by mouth (orally) twice daily Other names: TUKYSA, ONT-380, ARRY-380 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: Herceptin 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.
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: Avastin 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: Erbitux 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.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232

Contact:
Vanderbilt Clinical Trials Inbox
800-811-8480
cip@vumc.org

More Details

Status: Recruiting
Sponsor: Seagen Inc.

Study Contact

Seagen Trial Information Support
866-333-7436
clinicaltrials@seagen.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.