Phase 3 N=2,034 Randomized Double-blind Treatment

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

Colorectal Cancer

Bottom Line

View on ClinicalTrials.gov: NCT00069095 ↗

Enrolled (actual)

2,034

Serious AEs

38.2%

Results posted

Jan 2016

Primary outcome: Primary: Progression-free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored): Non-inferiority of XELOX Versus FOLFOX-4 — 259; 241 days

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Oxaliplatin 130 mg/m^2 (Drug); Capecitabine 1000 mg/m^2 (Drug); Bevacizumab 7.5 mg/kg (Drug); Placebo for bevacizumab 7.5 mg/kg (Drug); Oxaliplatin 85 mg/m^2 (Drug); Leucovorin 200 mg/m^2 (Drug); Fluorouracil 400 mg/m^2 (Drug); Bevacizumab 5 mg/kg (Drug); Placebo for bevacizumab 5 mg/kg (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Hoffmann-La Roche
Primary completion: Jan 2006

Outcome Measures

Outcome	Result	p-value
PRIMARY Progression-free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored): Non-inferiority of XELOX Versus FOLFOX-4	259; 241	—
PRIMARY PFS as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	244.0; 285.0	0.0023 sig
SECONDARY PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Non-inferiority of XELOX Versus FOLFOX-4	304.0; 261.0	—
SECONDARY PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	259.0; 335.0	<0.0001 sig
SECONDARY PFS (On-treatment Approach): Non-inferiority of XELOX Versus FOLFOX-4	268.0; 234.0	—
SECONDARY PFS (On-treatment Approach): Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	241.0; 316.0	<0.0001 sig
SECONDARY PFS by General Approach, Participants With Curative Surgery Not Censored: Non-inferiority of XELOX Versus FOLFOX-4	260.0; 244.0	—
SECONDARY PFS by General Approach, Participants With Curative Surgery Not Censored: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	245.0; 287.0	0.0015 sig
SECONDARY Overall Survival: Non-inferiority of XELOX Versus FOLFOX-4	549.0; 577.0	—
SECONDARY Overall Survival: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	574.0; 551.0	0.1921
SECONDARY Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST): Non-inferiority of XELOX Versus FOLFOX-4	49.4; 46.4	—
SECONDARY Best Overall Response (BOR) as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	49.2; 46.5	0.3091
SECONDARY BOR as Assessed by the IRC According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4	38.6; 37.1	—
SECONDARY BOR as Assessed by the IRC According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	37.5; 37.5	0.9887
SECONDARY Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4	191.0; 179.0; 190.0; 176.0	—
SECONDARY Time to Treatment Failure as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	183.0; 209.0; 182.0; 208.0	0.0030 sig
SECONDARY Time to Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4	67; 93; 190; 191; 155; 110	—
SECONDARY Time to Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	58; 48; 146; 138; 105; 87	—
SECONDARY Duration of Overall Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4	239.0; 226.0	—
SECONDARY Duration of Overall Response as Assessed by the Investigator According to RECIST: Superiority Analysis of Chemotherapy Plus Bevacizumab Versus Chemotherapy Alone	225.0; 257.0	0.0307 sig
SECONDARY Duration of Complete Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4	347.0; 589.0	—
SECONDARY Duration of Complete Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone	403.0; 386.0	0.8207

Summary

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).

Eligibility Criteria

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00069095). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.