Patient accrual is under way at Ohio State for an interventional phase 1b clinical trial that will study side effects and best dose of the drug dasatinib in preventing oxaliplatin-induced peripheral neuropathy in patients with stage II, III and IV colorectal cancer and other gastrointestinal cancers who are receiving the FOLFOX regimen with or without bevacizumab.
Drugs used in chemotherapy, such as leucovorin, fluorouracil and oxaliplatin (the FOLFOX regimen), work to stop the growth of tumor cells by killing them, preventing them from dividing or keeping them from spreading. But a buildup of oxaliplatin in peripheral nerves can damage them and cause peripheral neuropathy, which results in numbness, tingling and pain, usually in the hands and feet. Dasatinib may prevent oxaliplatin from entering the nerve root and damaging it.
This study seeks to determine whether blocking the transporter of oxaliplatin using dasatinib will reduce oxaliplatin-induced peripheral neuropathy. The study was recently amended to allow inclusion of patients with stage II and III colon and rectal cancer or any other gastrointestinal cancers for which FOLFOX would be a suitable treatment.
Study design
Patients receive oxaliplatin 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 PO 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.
Primary objectives
To determine the recommended phase 2 dose of dasatinib in combination with oxaliplatin and fluorouracil (5FU) (modified version 6 regimen of leucovorin, fluorouracil and oxaliplatin [mFOLFOX6]) with or without bevacizumab in patients with metastatic colorectal cancer or other gastrointestinal cancers, defined as the lowest intermittent dose of dasatinib that affects serum biomarkers of OCT2 without influencing the pharmacokinetic properties of oxaliplatin.
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 cancer and other gastrointestinal cancers.
Study leaders
Principal investigator is Anne Noonan, MD, associate professor in the Division of Medical Oncology at Ohio State and member of the Translational Therapeutics (TT) Program at the OSUCCC – James. Scientific lead is Shuiying Hu, PhD, assistant professor in the College of Pharmacy and a member of the TT Program.
At a Glance
Trial No.: OSU-19067
ClinicalTrials.gov Identifier: NCT04164069
PI: Anne Noonan, MD
Phone: 614-385-2039
Questions & Referrals: anne.noonan@osumc.edu or danielle.trunzo@osumc.edu
Eligibility
Inclusion criteria: Men and women 18 years of age or older; patients with confirmed stage II, III or IV (advanced/metastatic) colorectal cancer or other gastrointestinal cancers who are candidates for mFOLFOX6, with or without bevacizumab therapy; pathological confirmation of gastrointestinal cancer; patients may have had prior therapy for metastatic colorectal or other gastrointestinal cancer; Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Exclusion criteria: Pre-existing neuropathy of any type which is grade 2 or greater (grade 1 neuropathy is allowed), treatment with any other investigational agents within 4 weeks or 5 half-lives (whichever is longer) prior to the first dose of dasatinib; gastrointestinal (GI) disease or impairment of GI function that is likely to significantly alter the absorption of dasatinib.