A Study of Avastin (Bevacizumab) Plus Crossover Fluoropyrimidine-Based Chemotherapy in Patients With Metastatic Colorectal Cancer.

• ClinicalTrials.gov Identifier: NCT00700102
• Recruitment Status: Completed
• First Posted: June 18, 2008
• Results First Posted: July 30, 2015
• Last Update Posted: July 30, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: June 17, 2008
• First Posted Date: June 18, 2008
• Results First Submitted Date: July 2, 2015
• Results First Posted Date: July 30, 2015
• Last Update Posted Date: July 30, 2015
• Study Start Date: February 2006
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 2, 2015): Overall Survival: Time From Randomization to Death From Any Cause [ Time Frame: within 6.5 years ]
• Original Primary Outcome Measures (submitted: June 17, 2008): Progression-free survival [ Time Frame: Event driven ]

Current Secondary Outcome Measures (submitted: July 2, 2015)

• Overall Survival: Months From Time of First Line Therapy [ Time Frame: within approximately 9.6 years ]
• Participants With Progression Free Survival Event [ Time Frame: within 6.5 years ]
• Progression Free Survival: Time to Event [ Time Frame: within 6.5 years ]
• Response Rate: Percentage of Participants With Best Overall Response, Defined as Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST Criteria [ Time Frame: within 6.5 years ]
• Response Rate: Participants With Response Status Based on RECIST Criteria [ Time Frame: within 6.5 years ]
  Response Evaluation Criteria In Solid Tumors (RECIST) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

Original Secondary Outcome Measures (submitted: June 17, 2008)

• Overall survival; response rate. [ Time Frame: Event driven ]
• AEs, laboratory parameters. [ Time Frame: Throughout study ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Avastin (Bevacizumab) Plus Crossover Fluoropyrimidine-Based Chemotherapy in Patients With Metastatic Colorectal Cancer.
• Official Title: A Randomized, Open-label Phase III Intergroup Study: Effect of Adding Bevacizumab to Cross Over Fluoropyrimidine Based Chemotherapy (CTx) in Patients With Metastatic Colorectal Cancer and Disease Progression Under First-line Standard CTx/Bevacizumab Combination
• Brief Summary: This study will evaluate the efficacy and safety of adding bevacizumab to crossover fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer who have experienced disease progression under first line treatment with standard chemotherapy plus bevacizumab. Participants will receive chemotherapy alone, or in combination with bevacizumab. The anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. Participants are allowed to continue on bevacizumab, even after stopping chemotherapy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Colorectal Cancer

Intervention

• Drug: Chemotherapy
  As prescribed
• Drug: Bevacizumab
  Bevacizumab, 5 mg/kg intravenously (IV) on days 1 and 14 of each 4 week cycle, or 7.5 mg/kg IV on days 1 and 22 of each 6 week cycle.
  Other Name: Avastin

Study Arms

• Active Comparator: Chemotherapy
  Chemotherapy alone until disease progression, unacceptable toxicity, or patient refusal
  Intervention: Drug: Chemotherapy
• Experimental: Chemotherapy + Bevacizumab
  Chemotherapy and Bevacizumab until disease progression, unacceptable toxicity, or patient refusal
  Interventions:

  • Drug: Chemotherapy
  • Drug: Bevacizumab

Publications *

• Kubicka S, Greil R, Andre T, Bennouna J, Sastre J, Van Cutsem E, von Moos R, Osterlund P, Reyes-Rivera I, Muller T, Makrutzki M, Arnold D; ML18147 study investigators including AIO, GERCOR, FFCD, UNICANCER GI, TTD, BGDO, GEMCAD, and AGMT groups. Bevacizumab plus chemotherapy continued beyond first progression in patients with metastatic colorectal cancer previously treated with bevacizumab plus chemotherapy: ML18147 study KRAS subgroup findings. Ann Oncol. 2013 Sep;24(9):2342-9. doi: 10.1093/annonc/mdt231. Epub 2013 Jul 12.
• Bennouna J, Sastre J, Arnold D, Osterlund P, Greil R, Van Cutsem E, von Moos R, Vieitez JM, Bouche O, Borg C, Steffens CC, Alonso-Orduna V, Schlichting C, Reyes-Rivera I, Bendahmane B, Andre T, Kubicka S; ML18147 Study Investigators. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013 Jan;14(1):29-37. doi: 10.1016/S1470-2045(12)70477-1. Epub 2012 Nov 16.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 2, 2015): 820
• Original Estimated Enrollment (submitted: June 17, 2008): 808
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult patients, >=18 years of age
• Metastatic colorectal cancer and disease progression
• Previously treated with first-line chemotherapy plus Avastin
• Eastern Cooperative Oncology Group (ECOG) performance status <=2.

Exclusion Criteria:

• Diagnosis of progression of disease more than 3 months after last Avastin administration
• First-line patients with progression-free survival in first-line of <3 months
• Patients receiving less than 3 consecutive months of Avastin in first-line therapy
• Past or current history (within the last 2 years prior to treatment start) of other malignancies, except for curatively treated basal and squamous cell cancer of the skin or in situ cancer of the cervix
• Clinically significant cardiovascular disease within 6 months prior to start of study treatment
• Known central nervous system (CNS) disease, except for treated CNS metastases as defined by protocol

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Netherlands, Norway, Portugal, Saudi Arabia, Spain, Sweden, Switzerland
• Removed Location Countries: Brazil, United States

Administrative Information

• NCT Number: NCT00700102
• Other Study ID Numbers: ML18147; 2006-004634-32 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Clinical Trials, Study Director, Hoffmann-La Roche
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: July 2015