Dose Dense Therapy and Bevacizumab in Solid Tumors and Colorectal Cancer

NCT ID: NCT00296062

Last Updated: 2012-01-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2011-05-31

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

bevacizumab

Phase II: IV over 30-90 minutes on days 1 and 15 of each course.

Intervention Type: BIOLOGICAL

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)

Intervention Type: 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)

Intervention Type: 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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• No significant traumatic injury within the past 28 days (phase II)
• No serious or nonhealing wound, ulcer, or bone fracture (phase II)
• No peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered (phase I)
• At least 2 weeks since prior immunotherapy or biologic therapy and recovered (phase I)
• No prior treatment for advanced or metastatic colorectal cancer (phase II)
• More than 12 months since prior adjuvant chemotherapy and/or biologic therapy (e.g., bevacizumab or cetuximab) and recovered (phase II)
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to the only site of measurable disease unless there is measurable disease progression within the radiation port after completion of radiotherapy
• No prior radiotherapy to ≥ 20% of the bone marrow
• More than 28 days since prior major surgical procedure* or open biopsy and recovered (phase II)
• More than 14 days since prior minor surgery* and recovered (phase II)
• Concurrent full-dose anticoagulation (e.g., warfarin) allowed provided the following criteria are met (phase II):

• Patient has an in-range INR (between 2 and 3) and is on a stable dose of oral anticoagulants or a stable dose of low molecular weight heparin
• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., known varices)
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No concurrent sargramostim (GM-CSF) NOTE: *Insertion of a vascular device is not considered major or minor surgery

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Smitha Krishnamurthi, MD

Role: PRINCIPAL_INVESTIGATOR

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Locations

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

U01CA062502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA043703

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CASE1205

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-7325

Identifier Type: OTHER

Identifier Source: secondary_id

CASE1205

Identifier Type: -

Identifier Source: org_study_id