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

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01652482
• Other study ID #: GO28074
• Secondary ID: 2011-005547-27
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2012
• Last updated: November 1, 2016
• Start date: October 2012
• Est. completion date: November 2014

Study information

• Verified date: November 2016
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 135
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

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.
• 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.
• 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.
• 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.
• MEHD7945A
MEHD7945A 1100 milligram (mg) intravenous infusion every 2 weeks until documented disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  Italy,  New Zealand,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria		approximately 2 year	No
Secondary	Plasma Concentration of 5-Fluorouracil		Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4	No
Secondary	Plasma Concentration of Irinotecan		Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4	No
Secondary	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)	No
Secondary	Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria		approximately 2 year	No
Secondary	Duration of Objective Response According to Modified RECIST v1.1 Criteria		approximately 2 year	No
Secondary	Overall Survival (OS)		approximately 2 year	No
Secondary	Number of Participants With Adverse Events		approximately 2 year	No
Secondary	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)	No
Secondary	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)	No