NCT04164069

Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab

A Phase Ib Adaptive Study Dasatinib for the Prevention of Oxaliplatin-Induced Neuropathy in Patients With Metastatic Gastrointestinal Cancer Receiving FOLFOX Chemotherapy With or Without Bevacizumab

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (actual)
• Sponsor: Anne Noonan · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies side effects and best dose of dasatinib in preventing oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancers who are receiving FOLFOX regimen with or without 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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose (RP2D) 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 colon, rectal or other GI cancer, 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 cancer or other GI cancer. SECONDARY OBJECTIVES: 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.

Conditions

• Advanced Colorectal Carcinoma
• Metastatic Colorectal Carcinoma
• Stage IV Colorectal Cancer AJCC v8
• Stage IVA Colorectal Cancer AJCC v8
• Stage IVB Colorectal Cancer AJCC v8
• Stage IVC Colorectal Cancer AJCC v8
• Stage II Colon Cancer
• Stage II Rectal Cancer
• Stage III Colon Cancer
• Stage III Rectal Cancer
• Esophageal Cancer
• Pancreatic Cancer
• Bile Duct Cancer
• Gastric Cancer
• Gall Bladder Cancer
• Small Bowel Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Bevacizumab	Given IV
DRUG	Dasatinib	Given PO
DRUG	Fluorouracil	Given IV
DRUG	Leucovorin	Given IV
DRUG	Leucovorin Calcium	Given IV
DRUG	Oxaliplatin	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies

Timeline

• Start date: 2020-09-02
• Primary completion: 2023-06-22
• Completion: 2023-06-22
• First posted: 2019-11-15
• Last updated: 2024-12-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study