A Study of RO5083945 in Combination With FOLFIRI Versus FOLFIRI Plus Cetuximab or FOLFIRI Alone as Second Line Treatment in Patients With Metastatic Colorectal Cancer

A Randomized, Multicenter, Open-label Phase II Study of RO5083945 in Combination With FOLFIRI Versus FOLFIRI Plus Cetuximab or FOLFIRI Alone as Second Line Treatment in Patients With KRAS Wild-type or Mutant Metastatic Colorectal Cancer

This randomized, multicenter, open label study will evaluate the safety and efficacy of RO5083945 in combination with FOLFIRI as compared to FOLFIRI plus cetuximab or FOLFIRI alone as second line treatment in patients with metastatic colorectal cancer. Patients will be randomized to receive RO5083945 (1400 mg intravenously on Day 1 and Day 8 and every 2 weeks thereafter) plus FOLFIRI standard iv chemotherapy or FOLFIRI plus cetuximab (400 mg/m2 iv on Day 1 followed by 250 mg/m2 iv every week) or FOLFIRI alone. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: FOLFIRI; Drug: RO5083945; Drug: cetuximab

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2298
    • Port Macquarie, New South Wales, Australia, 2444
  • South Australia
    • Adelaide, South Australia, Australia, 5041
  • Victoria
    • Box Hill, Victoria, Australia, 3128
    • EAST Bentleigh, Victoria, Australia, VIC 3165
    • Frankston, Victoria, Australia, 3199
• Belgium
  • Bruxelles, Belgium, 1200
  • Bruxelles, Belgium, 1000
  • Edegem, Belgium, 2650
  • Gent, Belgium, 9000
  • Leuven, Belgium, 3000
• France
  • Bordeaux, France, 33075
  • Brest, France, 29200
  • Lille, France, 59037
  • Paris, France, 75679
  • Saint Herblain, France, 44805
  • Toulouse, France, 31059
• Germany
  • Essen, Germany, 45122
  • Hamburg, Germany, 20246
  • Hannover, Germany, 30625
  • Heidelberg, Germany, 69120
  • Herne, Germany, 44625
  • Regensburg, Germany, 93049
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
  • Lombardia
    • Milano, Lombardia, Italy, 20132
    • Milano, Lombardia, Italy, 20162
    • Milano, Lombardia, Italy, 20141
    • Pavia, Lombardia, Italy, 27100
• Poland
  • Olsztyn, Poland, 10-228
  • Szczecin, Poland, 70-111
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08907
  • Madrid, Spain, 28007
  • Madrid, Spain, 28050
  • Sevilla, Spain, 41013
  • Valencia, Spain, 46010
  • Barcelona
    • Sabadell, Barcelona, Barcelona, Spain, 08208
  • Cantabria
    • Santander, Cantabria, Spain, 39008
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • Belfast, United Kingdom, BT9 7AB
  • Bournemouth, United Kingdom, BH7 7DW
  • Cardiff, United Kingdom, CF14 2TL
  • Dorchester, United Kingdom, DT1 2JY
  • Glasgow, United Kingdom, G12 0YN
  • London, United Kingdom, SE1 9RT
  • London, United Kingdom, SW3 6JJ
  • London, United Kingdom, WC1E 6DD
  • Northwood, United Kingdom, HA6 2RN
  • Romford, United Kingdom, RM7 0AG
  • Weston Super Mare, United Kingdom, BS23 4TQ
• United States
  • California
    • Encinitas, California, United States, 92024
    • Highland, California, United States, 92346
    • La Jolla, California, United States, 92037
    • La Verne, California, United States, 91750
    • Los Angeles, California, United States, 90095
    • Los Angeles, California, United States, 90033
    • San Diego, California, United States, 92123
  • Illinois
    • Harvey, Illinois, United States, 60426
    • Skokie, Illinois, United States, 60076
    • Skokie, Illinois, United States, 60077
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
    • Durham, North Carolina, United States, 27710
    • Winston-Salem, North Carolina, United States, 27103
  • Pennsylvania
    • Sayre, Pennsylvania, United States, 18840
  • South Carolina
    • Greenville, South Carolina, United States, 29615
  • Tennessee
    • Memphis, Tennessee, United States, 38119

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Carcinoma of the colon and/or rectum
• Disease progression during or within 6 months of last dose of oxaliplatin containing first-line combination therapy for metastatic disease
• ECOG performance status 0-1
• Adequate hematological, renal and liver function

Exclusion Criteria:

• Prior treatment with monoclonal antibody/small molecule against epidermal growth factor receptor (EGFR)
• Prior treatment with irinotecan
• Radiotherapy within the last 4 weeks before first dose of study drug (except for limited field palliative radiotherapy for bone pain relief)
• CNS metastasis
• History of or active autoimmune disorders/conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KRAS WT A	Drug: FOLFIRI; standard iv chemotherapy; Drug: RO5083945; 1400 mg iv on Day 1 and Day 8, and every 2 weeks thereafter
Active Comparator: KRAS WT B	Drug: FOLFIRI; standard iv chemotherapy; Drug: cetuximab; 400 mg/m2 iv on Day 1, followed by 250 mg/m2 iv every week
Experimental: KRAS mutant A	Drug: FOLFIRI; standard iv chemotherapy; Drug: RO5083945; 1400 mg iv on Day 1 and Day 8, and every 2 weeks thereafter
Active Comparator: KRAS mutant B	Drug: FOLFIRI; standard iv chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival: tumour assessments by CT scan or MRI according to RECIST criteria	approximately 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate: tumour assessments by CT scan or MRI according to RECIST criteria	approximately 18 months
Duration of response: time from complete or partial response to disease progression or death	approximately 18 months
Clinical benefit rate: stable disease for >6 weeks, complete response or partial response; tumour assessments by CT scan or MRI according to RECIST criteria	approximately 18 months
Overall survival	approximately 18 months
Safety: Incidence of adverse events	approximately 18 months
Effect of concomitant FOLFIRI on pharmacokinetics of RO5083945 and vice versa	approximately 18 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: March 29, 2011
• First Submitted That Met QC Criteria: March 29, 2011
• First Posted (Estimate): March 30, 2011

Study Record Updates

• Last Update Posted (Actual): November 17, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: BP25438