Clinical trial NCT00778102: A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer.
Official title: A Multicentre Randomised Phase II Study to Assess the Safety and Resectability in Patients With Initially Unresectable Liver Metastases Secondary to Colorectal Cancer Receiving First-line Treatment Either With mFOLFOX-6 Plus Bevacizumab or FOLFOXIRI Plus Bevacizumab (OLIVIA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-10-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This 2 arm study will compare the resection rate of liver metastases and safety of surgery in patients with metastatic colorectal cancer and primarily unresectable liver metastases receiving treatment with Avastin in combination with 5-FU, leucovorin and oxaliplatin with irinotecan (FOLFOXIRI) or without irinotecan (mFOLFOX-6) as first line treatment. Patients will be randomized to receive Avastin (5mg/kg iv every 2 weeks) in combination with each of these two standard neoadjuvant chemotherapy regimens. The anticipated time on study treatment is until surgery, disease progression, unacceptable toxicity or patient refusal, and the target sample size is \<100 individuals.


Eligibility criteria: Inclusion Criteria:

* adult patients, \>=18 years of age;
* unresectable liver metastasis secondary to cancer of colon or rectum;
* scheduled for standard first line chemotherapy;
* ECOG performance score of 0 or 1;
* condition feasible for major abdominal surgery after first line treatment.

Exclusion Criteria:

* diagnosis of metastatic disease \>3 months prior to study entry;
* evidence of extrahepatic disease, diffuse peritoneal carcinosis or involvement of celiac lymph nodes;
* prior systemic or local treatment of metastatic disease;
* prior (neo)adjuvant chemotherapy/radiotherapy completed within 6 months prior to study entry;
* history or evidence of CNS disease unrelated to cancer.

Primary outcomes:
measure: Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor
timeFrame: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
Secondary outcomes:
measure: Time to Resection
timeFrame: Up to 5 years (at Screening; prior to each cycle, and within 7 days prior to surgery; and at time of surgery)
measure: Percentage of Participants With Histopathological Response
timeFrame: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
measure: Percentage of Participants With Complete or Major Histopathological Response
timeFrame: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery)
measure: Percentage of Participants Experiencing Relapse Following Curative Resection
timeFrame: Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)
measure: Relapse-Free Survival (RFS)
timeFrame: Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)
measure: Percentage of Participants Experiencing Death or Disease Progression
timeFrame: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2)
measure: Progression-Free Survival (PFS)
timeFrame: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2)
measure: Percentage of Participants Who Died
timeFrame: Up to 5 years (prior to each cycle, and within 7 days prior to surgery; at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)
measure: Overall Survival (OS)
timeFrame: Up to 5 years (prior to each cycle, and within 7 days prior to surgery; at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)
measure: Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0
timeFrame: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2)
measure: Time to Response
timeFrame: Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; 4 and 12 weeks after surgery; and at the end of Cycles 4 and 8 if assessed as R0 or R1, or every 6 weeks until progression or resectability if assessed as R2)
measure: Percentage of Participants With Complications Related to First Resective Surgery
timeFrame: Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)
measure: Percentage of Participants With Complications Related to Second Resective Surgery
timeFrame: Up to 5 years (at time of surgery; 48 hours and 4 and 12 weeks after surgery; within 4 weeks after completion of treatment; every 3 to 6 months for 1 year; then annually)
Other outcomes:
Locations:
city: Wien
country: Austria
city: Bordeaux
country: France
city: Creteil
country: France
city: Le Mans
country: France
city: Lille
country: France
city: Lyon
country: France
city: Montpellier
country: France
city: Villejuif
country: France
city: San Sebastian
country: Spain
state: Guipuzcoa
city: Palma de Mallorca
country: Spain
state: Islas Baleares
city: Santiago de Compostela
country: Spain
state: La Coruña
city: Girona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Sutton
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Cremolini C, Antoniotti C, Stein A, Bendell J, Gruenberger T, Rossini D, Masi G, Ongaro E, Hurwitz H, Falcone A, Schmoll HJ, Di Maio M. Individual Patient Data Meta-Analysis of FOLFOXIRI Plus Bevacizumab Versus Doublets Plus Bevacizumab as Initial Therapy of Unresectable Metastatic Colorectal Cancer. J Clin Oncol. 2020 Aug 20:JCO2001225. doi: 10.1200/JCO.20.01225. Online ahead of print.
citation: Gruenberger T, Bridgewater J, Chau I, Garcia Alfonso P, Rivoire M, Mudan S, Lasserre S, Hermann F, Waterkamp D, Adam R. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol. 2015 Apr;26(4):702-708. doi: 10.1093/annonc/mdu580. Epub 2014 Dec 23.