Back to resultsSafety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
5-fluorouracil
Cetuximab
Irinotecan
Leucovorin
MEHD7945A
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
FOLFIRI + Cetuximab
FOLFIRI + MEHD7945A
Arm Description
Outcomes
Primary Outcome Measures
Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria
Secondary Outcome Measures
Plasma Concentration of 5-Fluorouracil
Plasma Concentration of Irinotecan
Number of Participants With Anti-MEHD7945A Antibodies
Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria
Duration of Objective Response According to Modified RECIST v1.1 Criteria
Overall Survival (OS)
Number of Participants With Adverse Events
Maximum Observed Serum Concentration (Cmax) of MEHD7945A
Minimum Observed Serum Concentration (Cmin) of MEHD7945A
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01652482
Brief Title
Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
135 (Actual)
8. Arms, Groups, and Interventions
Arm Title
FOLFIRI + Cetuximab
Arm Type
Active Comparator
Arm Title
FOLFIRI + MEHD7945A
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
5-fluorouracil
Other Intervention Name(s)
ADRUCIL
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
CAMPTOSAR
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
WELLCOVORIN
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
MEHD7945A
Intervention Description
MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria
Time Frame
approximately 2 year
Secondary Outcome Measure Information:
Title
Plasma Concentration of 5-Fluorouracil
Time Frame
Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
Title
Plasma Concentration of Irinotecan
Time Frame
Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
Title
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)
Title
Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria
Time Frame
approximately 2 year
Title
Duration of Objective Response According to Modified RECIST v1.1 Criteria
Time Frame
approximately 2 year
Title
Overall Survival (OS)
Time Frame
approximately 2 year
Title
Number of Participants With Adverse Events
Time Frame
approximately 2 year
Title
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)
Title
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Genentech, Inc.
Official's Role
Study Director
Facility Information:
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
City
San Luis Obispo
State/Province
California
ZIP/Postal Code
93454
Country
United States
City
Santa Barbara
State/Province
California
ZIP/Postal Code
93105
Country
United States
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
City
Orange Park
State/Province
Florida
ZIP/Postal Code
32073
Country
United States
City
Harvey
State/Province
Illinois
ZIP/Postal Code
60426
Country
United States
City
Paducah
State/Province
Kentucky
ZIP/Postal Code
42003
Country
United States
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
City
Jefferson City
State/Province
Missouri
ZIP/Postal Code
65109
Country
United States
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89148
Country
United States
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
City
New Lambton Heights
State/Province
New South Wales
ZIP/Postal Code
2305
Country
Australia
City
St. Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
City
Wollongong
State/Province
New South Wales
ZIP/Postal Code
2500
Country
Australia
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5041
Country
Australia
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
City
Charleroi
ZIP/Postal Code
B6000
Country
Belgium
City
Haine-Saint-Paul
ZIP/Postal Code
7100
Country
Belgium
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
City
Liège
ZIP/Postal Code
4000
Country
Belgium
City
Creteil
ZIP/Postal Code
94000
Country
France
City
Lyon
ZIP/Postal Code
69373
Country
France
City
Paris
ZIP/Postal Code
75015
Country
France
City
Villejuif
ZIP/Postal Code
94805
Country
France
City
Dresden
ZIP/Postal Code
01307
Country
Germany
City
München
ZIP/Postal Code
81737
Country
Germany
City
München
ZIP/Postal Code
81925
Country
Germany
City
Stuttgart
ZIP/Postal Code
70199
Country
Germany
City
Trier
ZIP/Postal Code
54290
Country
Germany
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20133
Country
Italy
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20162
Country
Italy
City
Orbassano
State/Province
Piemonte
ZIP/Postal Code
10043
Country
Italy
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56100
Country
Italy
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
City
Auckland
ZIP/Postal Code
1142
Country
New Zealand
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
City
Dunedin
ZIP/Postal Code
9001
Country
New Zealand
City
Tauranga
ZIP/Postal Code
3112
Country
New Zealand
City
Brasov
ZIP/Postal Code
500091
Country
Romania
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
City
Bucuresti
ZIP/Postal Code
030171
Country
Romania
City
Iasi
ZIP/Postal Code
700106
Country
Romania
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
City
Madrid
ZIP/Postal Code
28007
Country
Spain
City
Madrid
ZIP/Postal Code
28050
Country
Spain
City
Valencia
ZIP/Postal Code
46010
Country
Spain
City
Aberdeen
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
City
Oxford
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
City
Wirral
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29506988
Citation
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.
Results Reference
derived
Learn more about this trial
Safety and Efficacy Study of MEHD7945A + FOLFIRI Versus Cetuximab + FOLFIRI as Second Line Therapy in Participants With KRAS Wild-Type Metastatic Colorectal Cancer (mCRC)
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