Recruiting

Phase 3

Tucatinib & Trastuzumab, mFOLFOX6A Study of Tucatinib With Trastuzumab and mFOLFOX6 Versus Standard of Care Treatment in First-line HER2+ Metastatic Colorectal Cancer

Sponsor:

Seagen, a wholly owned subsidiary of Pfizer

Code:

NCT05253651

Conditions

Colorectal Neoplasms

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

tucatinib

trastuzumab

bevacizumab

cetuximab

oxaliplatin

Study Details

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 determine 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.

Conditions

Colorectal Neoplasms

Study ID

NCT05253651

Start date

Oct 24, 2022

Status verified date

Jul, 2026

Completion date

Jul 3, 2030

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 locally advanced unresectable or 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
Active or untreated gastrointestinal (GI) perforation at the time of screening.

Study Design

Enrollment

400 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Tucatinib Arm

Tucatinib + trastuzumab + mFOLFOX6

active comparator: Standard of Care Arm

Either (1) mFOLFOX6, (2) mFOLFOX6 and bevacizumab, or (3) mFOLFOX6 and cetuximab

Interventions

tucatinib

300mg given by mouth (orally) twice daily

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.

bevacizumab

5mg/kg given by IV every 2 weeks

cetuximab

400mg/m2 loading dose will be given by IV on Cycle 1 day 1, followed by 250mg/m2 given by IV weekly

oxaliplatin

85mg/m2 given by IV every 2 weeks. Component of mFOLFOX6.

leucovorin

400mg/ m2 given by IV every 2 weeks. Component of mFOLFOX6.

levoleucovorin

200mg/ m2 given by IV every 2 weeks. May be given in place of leucovorin. Component of mFOLFOX6.

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.

Primary outcome measure

Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 3 years ]

Central Contacts and Locations

Central contacts

Pfizer CT.gov Call Center

1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations

Palo Verde Hematology Oncology

Recruiting

Glendale, Arizona, United States, 85304

Mayo Clinic Building - Phoenix

Recruiting

Phoenix, Arizona, United States, 85054

Mayo Clinic Hospital

Recruiting

Phoenix, Arizona, United States, 85054

Mayo Clinic

Recruiting

Scottsdale, Arizona, United States, 85259

Los Angeles Cancer Network - Anaheim

Recruiting

Anaheim, California, United States, 92801

Los Angeles Cancer Network - Fountain Vally

Recruiting

Fountain Valley, California, United States, 92708

Los Angeles Cancer Network - Corporate Office

Recruiting

Glendale, California, United States, 91204

Los Angeles Hematology Oncology Medical Group

Recruiting

Glendale, California, United States, 91204

Los Angeles Hematology Oncology Medical Group

Recruiting

Glendale, California, United States, 91206

Los Angeles Hematology Oncology Medical Group

Recruiting

Los Angeles, California, United States, 90017

Los Angeles Hematology Oncology Medical Group

Recruiting

Pasadena, California, United States, 91105

Los Angeles Hematology Oncology Medical Group

Recruiting

Van Nuys, California, United States, 91405