This phase Ib trial studies side effects and best dose of dasatinib in preventing oxaliplatin-induced peripheral neuropathy in patients with stage II-IV colon or rectal cancer or other gastrointestinal cancers who are receiving FOLFOX regimen and bevacizumab. Drugs used in chemotherapy, such as leucovorin, fluorouracil, and oxaliplatin (FOLFOX regimen), work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. However, the buildup of oxaliplatin in the cranial nerves can result in damage or the nerves. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Blocking these enzymes may reduce oxaliplatin-induced peripheral neuropathy.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04164069.
PRIMARY OBJECTIVES:
I. To determine the recommended phase 2 dose (RP2D) of dasatinib in combination with oxaliplatin and fluorouracil (5FU) (modified folinic acid-fluorouracil-oxaliplatin-6 regimen [mFOLFOX6]) with or without bevacizumab in patients with stage II, III or IV colon or rectal cancer and other gastrointestinal cancers who are candidates for mFOLFOX6, defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2 without influencing the pharmacokinetic properties of oxaliplatin.
II. To determine the toxicity profile (based on Chemotherapy-Induced Peripheral Neuropathy [CIPN]20 and Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0) of dasatinib in combination with oxaliplatin/5-FU/bevacizumab in patients with colorectal and other gastrointestinal (GI) cancers.
SECONDARY OBJECTIVE:
I. To evaluate the influence of dasatinib on the pharmacokinetics of oxaliplatin and vice versa in these patients.
OUTLINE: This is a dose-escalation study of dasatinib.
Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin IV over 2 hours, fluorouracil slow IV push over 2-4 minutes followed by continuous infusion over 46 hours on days 1 and 15. Patients also receive dasatinib orally (PO) once daily (QD) on days 14, 15, and 28 of cycle 1 and day 1 of cycle 2. Patients may receive bevacizumab IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to cycle 3 day 1 in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples on study.
Lead OrganizationOhio State University Comprehensive Cancer Center
Principal InvestigatorAnne Mary Noonan