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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01652482
First received: July 26, 2012
Last updated: July 21, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Colorectal Cancer
Drug: 5-fluorouracil
Drug: Cetuximab
Drug: Irinotecan
Drug: Leucovorin
Drug: MEHD7945A
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria [ Time Frame: approximately 2 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma Concentration of 5-Fluorouracil [ Time Frame: Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4 ] [ Designated as safety issue: No ]
  • Plasma Concentration of Irinotecan [ Time Frame: Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4 ] [ Designated as safety issue: No ]
  • Number of Participants With Anti-MEHD7945A Antibodies [ Time Frame: Pre-dose on Day 1 Cycles 1, 4, and 8; treatment completion visit (up to approximately 2 years) ] [ Designated as safety issue: No ]
  • Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria [ Time Frame: approximately 2 year ] [ Designated as safety issue: No ]
  • Duration of Objective Response According to Modified RECIST v1.1 Criteria [ Time Frame: approximately 2 year ] [ Designated as safety issue: No ]
  • Overall Survival (OS) [ Time Frame: approximately 2 year ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events [ Time Frame: approximately 2 year ] [ Designated as safety issue: No ]
  • Maximum Observed Serum Concentration (Cmax) of MEHD7945A [ Time Frame: 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) ] [ Designated as safety issue: No ]
  • Minimum Observed Serum Concentration (Cmin) of MEHD7945A [ Time Frame: Pre-dose on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year) ] [ Designated as safety issue: No ]

Enrollment: 135
Study Start Date: October 2012
Study Completion Date: November 2014
Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: WELLCOVORIN
Drug: MEHD7945A
MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01652482

  Hide Study Locations
Locations
United States, California
Bakersfield, California, United States, 93309
Fullerton, California, United States, 92835
Los Angeles, California, United States, 90033
Los Angeles, California, United States, 90095
San Luis Obispo, California, United States, 93454
Santa Barbara, California, United States, 93105
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Orange Park, Florida, United States, 32073
United States, Illinois
Harvey, Illinois, United States, 60426
United States, Kentucky
Paducah, Kentucky, United States, 42003
United States, Maryland
Rockville, Maryland, United States, 20850
United States, Massachusetts
Boston, Massachusetts, United States, 02114
Boston, Massachusetts, United States, 02215
United States, Michigan
Detroit, Michigan, United States, 48201
United States, Missouri
Jefferson City, Missouri, United States, 65109
United States, Nevada
Las Vegas, Nevada, United States, 89148
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
Kirkland, Washington, United States, 98034
Seattle, Washington, United States, 98109
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
Australia, Queensland
Herston, Queensland, Australia, 4029
Southport, Queensland, Australia, 4215
Australia, South Australia
Adelaide, South Australia, Australia, 5041
Australia, 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
Milano, Lombardia, Italy, 20133
Milano, Lombardia, Italy, 20162
Orbassano, Piemonte, Italy, 10043
Pisa, Toscana, Italy, 56100
Padova, Veneto, Italy, 35128
New Zealand
Auckland, New Zealand, 1142
Christchurch, New Zealand, 8011
Dunedin, New Zealand, 9001
Tauranga, New Zealand, 3143
Romania
Brasov, Romania, 500091
Bucharest, Romania, 022328
Bucuresti, Romania, 030171
Iasi, Romania, 700106
Spain
Barcelona, Spain, 08035
Barcelona, Spain, 08036
Madrid, Spain, 28050
Madrid, Spain, 28007
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
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01652482     History of Changes
Other Study ID Numbers: GO28074  2011-005547-27 
Study First Received: July 26, 2012
Last Updated: July 21, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Cetuximab
Fluorouracil
Immunoglobulin G
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2016