An Open-Label Randomized Phase III Study of Intermittent Oral Capecitabine in Combination with Intravenous Oxaliplatin (Q3W) (XELOX”) versus Bolus and Continuous Infusion Fluorouracil/Intravenous Leucovorin with Intravenous Oxaliplatin (Q2W) (FOLFOX4”) as Treatment for Patients with Metastatic Colorectal Cancer who have Received Prior Treatment with CPT- 11 in Combination with 5-FU/LV as First Line Therapy.

Phase 1

• Registration Number: EUCTR2004-001685-40-SK
• Lead Sponsor: Hoffmann-La Roche Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2004-10-20
• Last Update Posted: 5 June 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 610

Inclusion Criteria

*) Male or female outpatients aged >= 18 years.
*) Be ambulatory and have a ECOG performance status of <=2.
*) Histologically confirmed adenocarcinoma of the colon or rectum with metastatic disease.
*) Patients whose disease has recurred or progressed during or within 6 months of completion of first line therapy with the combination of CPT-11 and 5-FU/LV, or patients stopping first line CPT-11/5-FU/LV combination therapy due to excessive toxicity within the first 8 weeks, as judged by the treating physician.
*) First line CPT-11 + 5-FU/LV may include the following:
- CPT11 + 5-FU/LV
- CPT11 + 5-FU (if infusional 5-FU)
- CPT11 + 5-FU/LV + concomitant (not sequential) targeted biological agent
•
*) Previous chemotherapy (i.e., CPT-11 and 5-FU/LV) must have been completed at least 3 weeks prior to randomization and any acute/delayed toxicity must have resolved.
*) Prior radiotherapy is permitted if it was not administered to target lesions selected for this study, unless progression of the selected target lesions within the radiation portal is documented, and provided it has been completed at least 4 weeks before randomization.
*) At least one unidimensionally measurable lesion with a diameter >20 mm using conventional CT or MRI scans or >10 mm using spiral CT scans (use of spiral CT must be documented in medical records.
*) Have a life expectancy of at least 3 months.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

*) Received more than one prior chemotherapeutic or other systemic anti-cancer treatment regimen in the metastatic setting.
*) Prior active or passive immunotherapy for metastatic disease, unless in combination with first line CPT-11 + 5-FU/LV.
*) Prior treatment with oxaliplatin.
*) Pregnant or lactating women.
*) Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.
*) Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study.
*) History of another malignancy within the last five years except cured basal cell carcinoma of skin and cured carcinoma in-situ of uterine cervix.
*) History or evidence upon physical examination of CNS disease (e.g., primary brain tumor, seizure not controlled with standard medical therapy, any brain metastases, or history of stroke).
*) History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for oral drug intake.
*) Clinically significant (i.e. active) cardiovascular disease e.g. uncontrolled hypertension, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or grade II or greater peripheral vascular. In addition patients with myocardial infarction within 1 year prior to study treatment start will be excluded (see appendix 10).
*) Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
*) Interstitial pneumonia or extensive symptomatic fibrosis of the lungs.
*) Known peripheral neuropathy ? NCI CTC grade 1. Absence of deep tendon reflexes (DTRs) as the sole neurologic abnormality does not render the patient ineligible.
*) Organ allografts requiring immunosuppressive therapy.
*) Serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease.
*) Moderate or severe renal impairment [creatinine clearance equal to or below 50 mL/min (calculated according to Cockroft and Gault, Appendix 3)], or serum creatinine > 1.5 x upper limit of normal (ULN).
*) Any of the following laboratory values:
•Absolute neutrophil count (ANC) < 1.5 x 109/L
•Platelet count < 100 x 109/L
•Total bilirubin > 1.5 x ULN
•ALAT, ASAT > 2.5 x ULN, or > 5 x (ULN) in case of liver metastases
*) Alkaline phosphatase > 2.5 x ULN, or > 5 x ULN in case of liver metastases, or > 10 x ULN in case of bone metastases.

*) Prior unanticipated severe reaction to fluoropyrimidine therapy, or known dihydropyrimidine dehydrogenase (DPD) deficiency.
*) Known hypersensitivity to platinum compounds or any of the components of the study medications.
*) Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified