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
2 other identifiers
interventional
135
10 countries
65
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 colorectal-cancer
Started Oct 2012
Shorter than P25 for phase_2 colorectal-cancer
65 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 26, 2012
CompletedFirst Posted
Study publicly available on registry
July 30, 2012
CompletedStudy Start
First participant enrolled
October 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2014
CompletedNovember 2, 2016
November 1, 2016
2.1 years
July 26, 2012
November 1, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria
approximately 2 year
Secondary Outcomes (9)
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
- +4 more secondary outcomes
Study Arms (2)
FOLFIRI + Cetuximab
ACTIVE COMPARATORFOLFIRI + MEHD7945A
EXPERIMENTALInterventions
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.
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.
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.
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.
MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Genentech, Inc.lead
Study Sites (65)
Unknown Facility
Bakersfield, California, 93309, United States
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Fullerton, California, 92835, United States
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Los Angeles, California, 90033, United States
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Los Angeles, California, 90095, United States
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San Luis Obispo, California, 93454, United States
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Santa Barbara, California, 93105, United States
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Aurora, Colorado, 80045, United States
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Orange Park, Florida, 32073, United States
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Harvey, Illinois, 60426, United States
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Paducah, Kentucky, 42003, United States
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Rockville, Maryland, 20850, United States
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Boston, Massachusetts, 02114, United States
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Boston, Massachusetts, 02215, United States
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Detroit, Michigan, 48201, United States
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Jefferson City, Missouri, 65109, United States
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Las Vegas, Nevada, 89148, United States
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Philadelphia, Pennsylvania, 19104, United States
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Kirkland, Washington, 98034, United States
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Seattle, Washington, 98109, United States
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Darlinghurst, New South Wales, 2010, Australia
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New Lambton Heights, New South Wales, 2305, Australia
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St Leonards, New South Wales, 2065, Australia
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Sydney, New South Wales, 2217, Australia
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Waratah, New South Wales, 2298, Australia
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Wollongong, New South Wales, 2500, Australia
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Herston, Queensland, 4029, Australia
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Southport, Queensland, 4215, Australia
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Adelaide, South Australia, 5041, Australia
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Frankston, Victoria, 3199, Australia
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Brussels, 1200, Belgium
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Charleroi, B6000, Belgium
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Haine-Saint-Paul, 7100, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Créteil, 94000, France
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Lyon, 69373, France
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Paris, 75015, France
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Villejuif, 94805, France
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Dresden, 01307, Germany
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München, 81737, Germany
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München, 81925, Germany
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Stuttgart, 70199, Germany
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Trier, 54290, Germany
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Milan, Lombardy, 20133, Italy
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Milan, Lombardy, 20162, Italy
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Orbassano, Piedmont, 10043, Italy
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Pisa, Tuscany, 56100, Italy
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Padua, Veneto, 35128, Italy
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Auckland, 1142, New Zealand
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Christchurch, 8011, New Zealand
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Dunedin, 9001, New Zealand
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Tauranga, 3112, New Zealand
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Brasov, 500091, Romania
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Bucharest, 022328, Romania
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Bucharest, 030171, Romania
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Iași, 700106, Romania
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Barcelona, Barcelona, 08035, Spain
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Barcelona, Barcelona, 08036, Spain
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Madrid, Madrid, 28007, Spain
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Madrid, Madrid, 28050, Spain
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Valencia, Valencia, 46010, Spain
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Aberdeen, AB25 2ZN, United Kingdom
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London, NW1 2BU, United Kingdom
Unknown Facility
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Unknown Facility
Oxford, OX3 7LJ, United Kingdom
Related Publications (1)
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.
PMID: 29506988DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Genentech, Inc.
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 26, 2012
First Posted
July 30, 2012
Study Start
October 1, 2012
Primary Completion
November 1, 2014
Study Completion
November 1, 2014
Last Updated
November 2, 2016
Record last verified: 2016-11