A Phase I Trial Evaluating mFOLFOX6 and Avastin With Nexavar as First-Line Treatment for Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

Official title: A Phase I Trial Evaluating mFOLFOX6 and Avastin With Nexavar as First-Line Treatment for Metastatic Colorectal Cancer

Status Terminated

Clinical Trial Summary

This research study is being performed at approximately 3 sites associated with Accelerated Community Oncology Research Network, Inc. (ACORN). Approximately 45 subjects will take part in this study.

In this study, everyone will receive the same dose of mFOLFOX6 and Avastin. There will be five groups of subjects. Each group of subjects will receive a higher dose of Nexavar than the previous group. This will continue until a subject group has a major side effects from the dose they are given. This is so that the sponsor can determine the highest dose of Nexavar that can be used with mFOLFOX6 and AVastin (this is called the maximum tolerated dose or MTD).

Clinical Trial Description

This is an investigator-initiated, multicenter, network, Phase 1, open-label, dose-ranging study. The maximum sample size will be 45 patients (up to 30 patients for determining MTD at Phase I, and an additional 15 patients to provide for estimate of progression free survival). All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle. Treatment cycle length is 2 weeks (Q2W). Sorafenib will be administered daily throughout treatment beginning on day 1.

Dose limiting toxicity will be defined as any grade 4 hematologic event or any grade 3 or 4 non-hematologic event occurring during cycle 1 or 2 that is attributable to sorafenib or the combination. The following events are excluded from this definition: grade 3 nausea and/or vomiting responsive to antiemetics; grade 3 fever or infection; grade 3 diarrhea responsive to antidiarrheal therapy.

Three patients will be enrolled at a dose level and observed for dose-limiting toxicities (DLTs) for 2 cycles of treatment. Dose escalation for sorafenib will depend on the number of patients experiencing DLT(s) as follows:

• If 0/3 patients experience DLT(s), then 3 more patients are treated at the next higher dose.

• If 1/3 patients experiences DLT(s), then 3 more patients are enrolled at that dose. If 1/6 of the patients treated at that dose experiences DLT(s), then the next cohort is treated at the next higher dose. However, if ≥2/6 patients experience DLT(s) at that dose, then the MTD is considered to have been exceeded. At that point, 3 more patients are treated at the next lower dose, unless 6 have already been treated at that lower dose.

• If ≥2/3 patients experience DLT(s) at a dose, then 3 more patients are enrolled at the next lower dose unless 6 patients have already been treated at that dose.

Dose escalation will continue until the MTD is determined or until all dose levels have been completed. The MTD is defined as the dose at which ≤1 of 6 patients experience DLT(s), and above which ≥2 of 6 patients experience DLT(s). If the MTD is at Dose Level 2 (or lower), then the study will be terminated and no further patients will be enrolled.

Once the MTD for sorafenib combined with mFOLFOX6 and bevacizumab has been determined, an additional 15 patients with mCRC will be enrolled into an extension of the Phase 1 study. These patients will be treated at the MTD for sorafenib with the combination therapy to assess PFS and safety of the regimen as first-line therapy in mCRC. All patients will be eligible for indefinite treatment in the absence of disease progression or unacceptable toxicity. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

• NCT number: NCT00779311
• Study type: Interventional
• Source: Accelerated Community Oncology Research Network
• Status: Terminated
• Phase: Phase 1
• Start date: October 2008
• Completion date: March 2011