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
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.
- 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
- 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
- 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
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase II: Bevacizumab plus 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
Courses repeat every 28 days in the absence of unacceptable toxicity.
Smitha Krishnamurthi, MD
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
United States: Federal Government
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|