Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)

A Phase II, Multicenter, Open-Label, Randomized Study Evaluating the Efficacy and Safety of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI in Second Line in Patients With KRAS Wildtype Metastatic Colorectal Cancer

This open-label, randomized, multicenter, Phase 2 study will evaluate the safety and efficacy of MEHD7945A when combined with FOLFIRI (folinic acid [leucovorin], 5-fluorouracil [5-FU], and irinotecan) chemotherapy as compared to cetuximab plus FOLFIRI in participants with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) wild-type mCRC who have progressed after first-line oxaliplatin-containing chemotherapy for metastatic disease. Participants will be randomized to receive FOLFIRI chemotherapy plus either MEHD7945A or cetuximab. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: 5-fluorouracil; Drug: Cetuximab; Drug: Irinotecan; Drug: Leucovorin; Drug: MEHD7945A

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
    • New Lambton Heights, New South Wales, Australia, 2305
    • St. Leonards, New South Wales, Australia, 2065
    • Sydney, New South Wales, Australia, 2217
    • Waratah, New South Wales, Australia, 2298
    • Wollongong, New South Wales, Australia, 2500
  • Queensland
    • Herston, Queensland, Australia, 4029
    • Southport, Queensland, Australia, 4215
  • South Australia
    • Adelaide, South Australia, Australia, 5041
  • Victoria
    • Frankston, Victoria, Australia, 3199
• Belgium
  • Bruxelles, Belgium, 1200
  • Charleroi, Belgium, B6000
  • Haine-Saint-Paul, Belgium, 7100
  • Leuven, Belgium, 3000
  • Liège, Belgium, 4000
• France
  • Creteil, France, 94000
  • Lyon, France, 69373
  • Paris, France, 75015
  • Villejuif, France, 94805
• Germany
  • Dresden, Germany, 01307
  • München, Germany, 81925
  • München, Germany, 81737
  • Stuttgart, Germany, 70199
  • Trier, Germany, 54290
• Italy
  • Lombardia
    • Milano, Lombardia, Italy, 20133
    • Milano, Lombardia, Italy, 20162
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
  • Toscana
    • Pisa, Toscana, Italy, 56100
  • Veneto
    • Padova, Veneto, Italy, 35128
• New Zealand
  • Auckland, New Zealand, 1142
  • Christchurch, New Zealand, 8011
  • Dunedin, New Zealand, 9001
  • Tauranga, New Zealand, 3112
• Romania
  • Brasov, Romania, 500091
  • Bucharest, Romania, 022328
  • Bucuresti, Romania, 030171
  • Iasi, Romania, 700106
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Madrid, Spain, 28007
  • Madrid, Spain, 28050
  • Valencia, Spain, 46010
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • London, United Kingdom, NW1 2BU
  • Oxford, United Kingdom, OX3 7LJ
  • Wirral, United Kingdom, CH63 4JY
• United States
  • California
    • Bakersfield, California, United States, 93309
    • Fullerton, California, United States, 92835
    • Los Angeles, California, United States, 90095
    • Los Angeles, California, United States, 90033
    • San Luis Obispo, California, United States, 93454
    • Santa Barbara, California, United States, 93105
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Florida
    • Orange Park, Florida, United States, 32073
  • Illinois
    • Harvey, Illinois, United States, 60426
  • Kentucky
    • Paducah, Kentucky, United States, 42003
  • Maryland
    • Rockville, Maryland, United States, 20850
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02114
  • Michigan
    • Detroit, Michigan, United States, 48201
  • Missouri
    • Jefferson City, Missouri, United States, 65109
  • Nevada
    • Las Vegas, Nevada, United States, 89148
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
  • Washington
    • Kirkland, Washington, United States, 98034
    • Seattle, Washington, United States, 98109

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:

• Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum, with KRAS wild-type status
• Progressive disease on or after first-line oxaliplatin-containing regimen for mCRC; participants must have received oxaliplatin-containing chemotherapy for greater than or equal to (>/=) 3 months; no more than one prior chemotherapy regimen for metastatic disease is allowed
• Measurable disease per modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate hematologic and end-organ function

Exclusion Criteria:

• Prior treatment with irinotecan
• Prior treatment with an investigational or approved human epidermal growth factor receptor (HER)-targeted agent
• Last anti-tumor therapy within 4 weeks prior to Cycle 1, Day 1
• Leptomeningeal disease as the only manifestation of the current malignancy
• Active infection requiring intravenous antibiotics
• Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs
• Current severe, uncontrolled systemic disease
• Known human immunodeficiency virus (HIV) infection
• Untreated/active central nervous system metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
• Pregnant or lactating women
• Malignancies other than colorectal cancer within 5 years prior to randomization, except for adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FOLFIRI + Cetuximab	Drug: 5-fluorouracil; Standard 5-fluorouracil (5-FU) chemotherapy (400 milligram per square meter [mg/m^2] administered as intravenous bolus and then 5-FU 2400 mg/m^2 administered as continuous intravenous infusion over 46 +/- 2 hours) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.; Other Names: ADRUCIL; Drug: Cetuximab; Cetuximab 400 mg/m^2 intravenous infusion as a loading dose on Day 1 Cycle 1, followed by 250 mg/m^2 intravenous infusion weekly until documented disease progression or unacceptable toxicity.; Other Names: Erbitux; Drug: Irinotecan; Standard Irinotecan chemotherapy (180 milligram per square meter [mg/m^2] administered as intravenous infusion over 60 +/- 30 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.; Other Names: CAMPTOSAR; Drug: Leucovorin; Standard Leucovorin chemotherapy (400 mg/m^2 [racemic form] or 200 mg/m^2 [L-isomer form] administered by intravenous infusion over 120 +/- 10 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.; Other Names: WELLCOVORIN
Experimental: FOLFIRI + MEHD7945A	Drug: 5-fluorouracil; Standard 5-fluorouracil (5-FU) chemotherapy (400 milligram per square meter [mg/m^2] administered as intravenous bolus and then 5-FU 2400 mg/m^2 administered as continuous intravenous infusion over 46 +/- 2 hours) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.; Other Names: ADRUCIL; Drug: Irinotecan; Standard Irinotecan chemotherapy (180 milligram per square meter [mg/m^2] administered as intravenous infusion over 60 +/- 30 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.; Other Names: CAMPTOSAR; Drug: Leucovorin; Standard Leucovorin chemotherapy (400 mg/m^2 [racemic form] or 200 mg/m^2 [L-isomer form] administered by intravenous infusion over 120 +/- 10 minutes) or according to local standard-of-care prescribing information's, every 2 weeks until documented disease progression or unacceptable toxicity.; Other Names: WELLCOVORIN; Drug: MEHD7945A; MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria	approximately 2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentration of 5-Fluorouracil	Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
Plasma Concentration of Irinotecan	Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
Number of Participants With Anti-MEHD7945A Antibodies	Pre-dose on Day 1 Cycles 1, 4, and 8; treatment completion visit (up to approximately 2 years)
Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria	approximately 2 year
Duration of Objective Response According to Modified RECIST v1.1 Criteria	approximately 2 year
Overall Survival (OS)	approximately 2 year
Number of Participants With Adverse Events	approximately 2 year
Maximum Observed Serum Concentration (Cmax) of MEHD7945A	Pre-dose and 30 minutes after end of infusion on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)
Minimum Observed Serum Concentration (Cmin) of MEHD7945A	Pre-dose on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Hill AG, Findlay MP, Burge ME, Jackson C, Alfonso PG, Samuel L, Ganju V, Karthaus M, Amatu A, Jeffery M, Bartolomeo MD, Bridgewater J, Coveler AL, Hidalgo M, Kapp AV, Sufan RI, McCall BB, Hanley WD, Penuel EM, Pirzkall A, Tabernero J. Phase II Study of the Dual EGFR/HER3 Inhibitor Duligotuzumab (MEHD7945A) versus Cetuximab in Combination with FOLFIRI in Second-Line RAS Wild-Type Metastatic Colorectal Cancer. Clin Cancer Res. 2018 May 15;24(10):2276-2284. doi: 10.1158/1078-0432.CCR-17-0646. Epub 2018 Mar 5.

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: July 26, 2012
• First Submitted That Met QC Criteria: July 26, 2012
• First Posted (Estimate): July 30, 2012

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; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Leucovorin; Irinotecan; Cetuximab
• Other Study ID Numbers: GO28074; 2011-005547-27 (EudraCT Number)