A Study of Capecitabine (Xeloda) and Bevacizumab as a First-line Therapy in Patients With Metastatic Colorectal Cancer

Roche

Status and phase: Completed; Phase 3

Conditions: Colorectal Cancer

Treatments: Drug: Fluorouracil 400 mg/m^2; Drug: Capecitabine 1000 mg/m^2; Drug: Oxaliplatin 85 mg/m^2; Drug: Bevacizumab 5 mg/kg; Drug: Placebo for bevacizumab 5 mg/kg; Drug: Leucovorin 200 mg/m^2; Drug: Oxaliplatin 130 mg/m^2; Drug: Bevacizumab 7.5 mg/kg; Drug: Placebo for bevacizumab 7.5 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT00069095

NO16966

Details and patient eligibility

About

This 4 arm study assessed the efficacy and safety of oral capecitabine (Xeloda) or intravenous (iv) fluorouracil/leucovorin, in combination with iv oxaliplatin (Eloxatin) with or without iv bevacizumab (Avastin), as a first-line treatment in patients with metastatic colorectal cancer. Patients were randomized to receive 1) XELOX (Xeloda 1000 mg/m^2 orally [po] twice a day [bid] on Days 1-15 + oxaliplatin in 3 week cycles), 2) FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil [5-FU] in 2 week cycles), 3) XELOX + bevacizumab (7.5 mg iv on Day 1 in 3 week cycles), or 4) FOLFOX-4 + bevacizumab (5 mg iv on Day 1 in 2 week cycles).

Full description

This study was conducted in 2 parts: An initial 2-arm part in which patients were randomized to 1 of 2 different treatment groups (XELOX or FOLFOX-4), and a subsequent 2 x 2 factorial part, added to the study through a protocol amendment, in which additional patients were randomized into one of 4 different treatment groups (XELOX + placebo, FOLFOX-4 + placebo, XELOX + bevacizumab, or FOLFOX-4 + bevacizumab). Due to the comparison of the oral agent capecitabine with bolus and infused fluorouracil, the study was not blinded with respect to these 2 treatments. The study was double-blind with regard to the administration of bevacizumab, ie, there was a placebo control for bevacizumab in the second part of the study.

The study consisted of 3 phases, a Primary Study Treatment Phase, a Post-Study Treatment Phase, and a Follow-Up Phase.

Primary Study Treatment Phase

Patients were to receive up to 16 cycles (2-arm part of the study) or 24 cycles (4-arm part of the study) of treatment during the Primary Study Treatment Phase (48 weeks).

Post-Study Treatment Phase

Patients who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Patients who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the patient withdrew consent.

Follow-up Phase

Patients who terminated study treatment during the primary or post-study treatment phase were followed until disease progression or death.

Enrollment: 2,035 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients ≥ 18 years of age.
• Metastatic colorectal cancer.
• ≥ 1 target lesion.

Exclusion criteria

• Previous treatment with oxaliplatin or bevacizumab.
• Previous systemic chemotherapy or immunotherapy for advanced or metastatic disease.
• Progressive disease during or within 6 months of completion of previous adjuvant therapy.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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2,035 participants in 4 patient groups

XELOX (oxaliplatin+capecitabine)

Experimental group

Description:

Patients in the 2-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.

Treatment:

Drug: Oxaliplatin 130 mg/m^2

Drug: Placebo for bevacizumab 7.5 mg/kg

Drug: Capecitabine 1000 mg/m^2

XELOX (oxaliplatin+capecitabine) + bevacizumab

Experimental group

Description:

Patients in the 4-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle + bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.

Treatment:

Drug: Bevacizumab 7.5 mg/kg

Drug: Oxaliplatin 130 mg/m^2

Drug: Capecitabine 1000 mg/m^2

FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil)

Active Comparator group

Description:

Patients in the 2-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle.

Treatment:

Drug: Oxaliplatin 85 mg/m^2

Drug: Placebo for bevacizumab 5 mg/kg

Drug: Leucovorin 200 mg/m^2

Drug: Fluorouracil 400 mg/m^2

FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil) + bevacizumab

Active Comparator group

Description:

Patients in the 4-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv + bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle.

Treatment:

Drug: Oxaliplatin 85 mg/m^2

Drug: Bevacizumab 5 mg/kg

Drug: Leucovorin 200 mg/m^2

Drug: Fluorouracil 400 mg/m^2