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

  Show 65 Study Locations
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 21, 2016