The primary rationale for this study is to develop an optimized schedule of administration of FOLFOX + bevacizumab that maximizes the efficacy and safety of this regimen when administered to patients with advanced colorectal cancer. The hypothesis is that the use of an intermittent oxaliplatin (IO) schedule of FOLFOX/bevacizumab will allow these patients to continue on treatment for a longer period of time by reducing the proportion of patients who discontinue therapy early because of treatment-related toxicity and thus increasing the possibility of a longer time to progression.

Primary Objective:

• To test the hypothesis that an intermittent oxaliplatin (IO) schedule of FOLFOX/bevacizumab will allow patients to remain on therapy for a longer period of time compared to a conventional “treat-to-failure” schedule, by reducing the proportion of patients who discontinue therapy for treatment-related toxicity.

Secondary Objectives:

• To evaluate the impact of calcium/magnesium infusions on the incidence and severity of neurotoxicity in patients receiving either the IO or conventional FOLFOX/bevacizumab treatment schedules as first-line treatment for metastatic colorectal cancer.

• To evaluate the safety and efficacy of the IO versus the conventional schedule ± calcium and magnesium infusions, as part of oxaliplatin-based first-line therapy for metastatic colorectal cancer

Condition	Intervention	Phase
Colorectal Cancer	Drug: oxaliplatin	Phase IV

Further Study Details: 

Primary Outcomes: Primary Endpoint:; • Time to treatment failure (TTF) for the conventional oxaliplatin (CO) schedule in comparison with the intermittent oxaliplatin (IO) schedule.
Secondary Outcomes: Secondary Endpoint(s):; • The incidence of adverse events, including neurotoxicity, as determined using the NCI Common Toxicity Criteria version 3.0 (CTCAEv3.0).; • Quality of Life, including oxaliplatin-specific neurologic symptomsdetermined using the PNQoxali.; • The magnitude of changes in vibration thresholds as determined using calibrated fixed weight C64 Rydel-Seiffer Tuning Forks.; • Tumor response rate (overall and confirmed) based on application of the Response Evaluation Criteria in Solid Tumors (RECIST).; • Time to tumor progression (TTP).; • Time of tumor control (TTC), as discussed in Background and defined under Statistical Methods.; • Overall Survival (OS).; • Reasons for treatment discontinuation.; • For all secondary endpoints the main comparison will be between the CO and IO schedules. The effect of Ca/Mg on each of the tumor-specific endpoints will also be determined in a secondary analysis, as discussed in the Statistical Methods section

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• histologically or cytologically documented metastatic, measurable adenocarcinoma of the colon, rectum, or appendix with no prior therapies for metastatic disease. ECOG PS of 0 or 1. Adequate hematologic, renal, and hepatic function as defined by required baseline laboratory parameters. No other serious concomitant disease.

Exclusion Criteria:

• Peripheral neuropathy > Grade 1 at baseline. History of significant cerebrovascular, cardiovascular, or peripheral vascular disease. History of abdominal fistula, gastrointestinal perforation, intra-abdominalabscess, major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to start of study drug. Minor surgical procedure, fine needle aspiration, or core biopsy within 7 days prior to start of study drug. Serious, non-healing wound, ulcer, or bone fracture. Active gastroduodenal ulcer. Evidence of bleeding diathesis or coagulopathy. Significant history of bleeding within 6 months prior to registration.

Please refer to this study by ClinicalTrials.gov identifier  NCT00129870

Public Registry GMA       publicregistrygma@sanofi-aventis.com

Minnesota
      Western IRB, Rochester,  Minnesota,  United States; Recruiting

Study chairs or principal investigators

Gilbert Jirau-Lucca, M.S.,  Study Director,  Sanofi-Aventis   

Study ID Numbers:  L_9444
Last Updated:  August 12, 2005
Record first received:  August 10, 2005
ClinicalTrials.gov Identifier:  NCT00129870
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-08-23