NCT00296062

Dose Dense Therapy and Bevacizumab in Solid Tumors and Colorectal Cancer

Dose-Dense and Dose-Intense Alternating Irinotecan/Capecitabine and Oxaliplatin/Capecitabine: Phase I in Solid Tumors and Phase II With Bevacizumab a First-Line Therapy of Advanced Colorectal Cancer

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Drugs used in chemotherapy, such as capecitabine, irinotecan, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also block blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of capecitabine when given together with irinotecan and oxaliplatin with or without bevacizumab and to see how well they work in treating patients with metastatic or locally advanced colorectal cancer or other solid tumors that cannot be removed by surgery.

Detailed description

The study was originally intended to be Phase I/Phase II but it was terminated early because of toxicity of treatment and therefore never moved to the Phase II portion of the study. OBJECTIVES: * Determine the maximum tolerated dose (MTD) and dose-limiting toxicity of dose-dense and dose-intense capecitabine in combination with alternating full-dose irinotecan hydrochloride and oxaliplatin in patients with metastatic or locally advanced unresectable solid tumors. (phase I) * Characterize the safety of the MTD in patients ≥ 65 years of age treated with this regimen. (phase I) * Characterize the pharmacokinetics of this regimen in patients ≥ 65 years of age. (phase I) * Characterize the functional status of patients ≥ 65 years of age at baseline and after study treatment, in terms of performance status, independence in activities, comorbidities, risk of malnutrition, and underlying depression. (phase I) * Characterize the neurological status of all patients, in terms of muscle strength and sensation, at baseline and after study treatment. (phase I) * Determine the clinical antitumor response in patients treated with this regimen. (phase I) * Determine whether the addition of bevacizumab to dose-intense capecitabine in combination with alternating full-dose irinotecan hydrochloride and oxaliplatin as first-line treatment leads to an improved response rate in patients with metastatic colorectal cancer compared to that of published results of fluoropyrimidine/oxaliplatin, fluoropyrimidine/irinotecan/bevacizumab, and fluoropyrimidine/irinotecan regimens. (phase II) * Determine the toxicity of bevacizumab in combination with this regimen in patients with metastatic colorectal cancer. (phase II) OUTLINE: This is a multicenter, phase I dose-escalation study of capecitabine followed by a phase II study. * Phase I (all solid tumor patients): Patients receive oral capecitabine twice daily on days 1-7 and 15-21. Patients also receive irinotecan hydrochloride IV over 90 minutes on days 1 and 15 during course 1 and all subsequent odd-numbered courses and oxaliplatin IV over 2 hours on days 1 and 15 during course 2 and all subsequent even-numbered courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity Cohorts of 3-6 patients receive escalating doses of capecitabine (during both odd- and even-numbered courses) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients (with at least 1 patient \< 65 years of age) experience dose-limiting toxicity. At least 6 patients are treated at the MTD. * Phase II (colorectal cancer patients): Patients receive capecitabine (at the MTD determined in phase I) in combination with irinotecan hydrochloride (during odd-numbered courses) and oxaliplatin (during even-numbered courses) as in phase I. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15 of each course. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Conditions

• Colorectal Cancer
• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
BIOLOGICAL	bevacizumab	Phase II: IV over 30-90 minutes on days 1 and 15 of each course.
DRUG	capecitabine	Phase I: oral capecitabine twice daily on days 1-7 and 15-21.Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of capecitabine (during both odd- and even-numbered courses) until the maximum tolerated dose (MTD) is determined.Phase II:receive capecitabine (at the MTD determined in phase I(odd-numbered courses)
DRUG	irinotecan hydrochloride	Phase I: irinotecan hydrochloride IV over 90 minutes on days 1 and 15 during course 1 and all subsequent odd-numbered courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.Phase II: receive capecitabine (at the MTD determined in phase I) in combination with irinotecan hydrochloride (during odd-numbered courses)
DRUG	oxaliplatin	Phase I: oxaliplatin IV over 2 hours on days 1 and 15 during course 2 and all subsequent even-numbered courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Phase II: oxaliplatin (during even-numbered courses) as in phase I

Timeline

• Start date: 2006-03-01
• Primary completion: 2009-10-01
• Completion: 2011-05-01
• First posted: 2006-02-24
• Last updated: 2012-01-16

Locations

1 site across 1 country: United States