OPAL Study: A Study of Avastin (Bevacizumab) in Combination With FOLFOXIRI in Patients With Previously Untreated Metastatic Colorectal Cancer

An Open Label, Single-arm, Phase II Study to Evaluate the Efficacy and the Feasibility of Bevacizumab (Avastin) Based on a FOLFOXIRI Regimen Until Progression in Patients With Previously Untreated Metastatic Colorectal Carcinoma(OPAL-Study)

This single arm study will assess progression-free survival, feasibility of use and safety of Avastin in combination with 5-FU/FA, oxaliplatin and irinotecan (FOLFOXIRI) as first line treatment in patients with metastatic colorectal cancer. Patients will receive up to 12 bi-weekly cycles of Avastin (5mg/kg iv) in combination with this standard neoadjuvant chemotherapy regimen followed by up to 40 bi-weekly cycles with Avastin plus 5-FU/FA. The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: 5-FU; Drug: bevacizumab [Avastin]; Drug: irinotecan; Drug: leucovorin; Drug: oxaliplatin

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
  • Berlin, Germany, 13347
  • Bochum, Germany, 44791
  • Celle, Germany, 29221
  • Celle, Germany, 29223
  • Dessau-Roßlau, Germany, 06847
  • Freiburg, Germany, 79106
  • Fulda, Germany, 36043
  • Hamburg, Germany, 20246
  • Hamburg, Germany, 22087
  • Hannover, Germany, 30171
  • Leer, Germany, 26789
  • Magdeburg, Germany, 39130
  • Magdeburg, Germany, 39120
  • Nürnberg, Germany, 90419
  • Stade, Germany, 21680
  • Villingen-Schwenningen, Germany, 78052

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, 18-70 years of age;
• metastatic colorectal cancer scheduled for standard first line chemotherapy;
• at least 1 measurable lesion;
• ECOG performance score of 0 or 1.

Exclusion Criteria:

• prior chemotherapy for metastatic colorectal cancer;
• prior (neo)adjuvant chemotherapy/radiotherapy of a non-metastatic malignancy completed within 6 months prior to study entry;
• concomitant malignancies other CRC;
• history or evidence of CNS disease unrelated to cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: 5-FU; 3200mg/m2 continuous iv infusions, day 1 every 2 weeks; Drug: bevacizumab [Avastin]; 5mg/kg iv infusion, day 1 every 2 weeks; Drug: irinotecan; 165mg/m2 iv infusion, day 1 every 2 weeks; Drug: leucovorin; 200mg/m2 iv infusion, day 1 every 2 weeks; Drug: oxaliplatin; 85mg/m2 iv infusion, day 1 every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	assessed every 8 weeks up to week 102, 3-monthly during follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival; proportion of patients achieving R0 resectability; objective response rate (complete response [CR] and partial response [PR]); proportion of patients completing 12 cycles of chemotherapy.	assessed every 4 weeks up to week 102 and at the end of follow-up period
Proportion of patients with NCI-CTC grade 3-5 adverse events; adverse events, laboratory parameters, ECOG performance status.	Throughout study, laboratory analyses every 2 weeks, ECOG assessment every 8 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Stein A, Atanackovic D, Hildebrandt B, Stubs P, Brugger W, Hapke G, Steffens CC, Illerhaus G, Bluemner E, Stohlmacher J, Bokemeyer C. Upfront FOLFOXIRI+bevacizumab followed by fluoropyrimidin and bevacizumab maintenance in patients with molecularly unselected metastatic colorectal cancer. Br J Cancer. 2015 Sep 15;113(6):872-7. doi: 10.1038/bjc.2015.299. Epub 2015 Sep 3.

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): February 1, 2014
• Study Completion (Actual): February 1, 2014

Study Registration Dates

• First Submitted: July 6, 2009
• First Submitted That Met QC Criteria: July 15, 2009
• First Posted (Estimate): July 16, 2009

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Oxaliplatin; Bevacizumab; Leucovorin; Irinotecan
• Other Study ID Numbers: ML20514; 2008-001180-11