1. A Phase 1 Study of Cabozantinib and Trifluridine/Tipiracil in Metastatic Colorectal Adenocarcinoma
- Author
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Dayyani, Farshid, Balangue, Jasmine, Valerin, Jennifer, Keating, Matthew J, Zell, Jason A, Taylor, Thomas H, and Cho, May T
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Clinical Trials and Supportive Activities ,Cancer ,Colo-Rectal Cancer ,Digestive Diseases ,6.1 Pharmaceuticals ,Good Health and Well Being ,Humans ,Male ,Middle Aged ,Uracil ,Trifluridine ,Frontotemporal Dementia ,Colorectal Neoplasms ,Drug Combinations ,Antineoplastic Combined Chemotherapy Protocols ,Adenocarcinoma ,Neutropenia ,Anilides ,Pyridines ,Pyrrolidines ,Thymine ,Angiogenesis ,Axl ,cMET ,Recommended phase II dose ,Resistance ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
IntroductionThis study determined the safety and recommended phase 2 dose (RP2D) of the multikinase inhibitor cabozantinib in combination with trifluridine/tipiracil (FTD/TPI) in refractory metastatic colorectal carcinoma (mCRC).Patients and methodsSingle institution investigator-initiated phase 1 study using 3+3 design. Eligible mCRC patients had received prior standard regimens. Cabozantinib was given orally (p.o.) at 20 mg (dose level [DL] 0) or 40 mg (DL 1) daily on days 1-28, and FTD/TPI p.o. at 35 mg/m2 on days 1-5 and 8-12 every 28 days. Prophylactic growth-factor support was allowed.ResultsFifteen patients were enrolled. Median age 56 years (31-80), male (12/15), ECOG 0/1 = 9/6. Three patients were treated at DL 0 and another nine were treated at DL 1, none exhibiting a DLT. Most common any grade (G) treatment related adverse events (TRAE) were diarrhea (50%), nausea (42%), neutropenia (42%), fatigue (33%), and rash (25%). G3-4 TRAE were neutropenia (25%) and thrombocytopenia, hypokalemia, and weight loss (each 8%). No serious TRAE or G5 were reported. The RP2D was determined to be DL 1. Median PFS was 3.8 months (95% CI 1.9-6.8) and disease control rate was 86.7%.ConclusionThe combination of cabozantinib and FTD/TPI is feasible and tolerable at standard doses with the use of growth factors and showed encouraging clinical activity in refractory mCRC.ClinicaltrialsGOV: NCT04868773.
- Published
- 2024