Clinical trial NCT01652482: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-07-30
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-free Survival (PFS) According to Modified RECIST v1.1 Criteria
timeFrame: approximately 2 year
Secondary outcomes:
measure: Plasma Concentration of 5-Fluorouracil
timeFrame: Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
measure: Plasma Concentration of Irinotecan
timeFrame: Pre-dose, 1 hour and after end of infusion on Day 1 Cycles 1-4
measure: Number of Participants With Anti-MEHD7945A Antibodies
timeFrame: Pre-dose on Day 1 Cycles 1, 4, and 8; treatment completion visit (up to approximately 2 years)
measure: Number of Participants With Objective Response According to Modified RECIST v1.1 Criteria
timeFrame: approximately 2 year
measure: Duration of Objective Response According to Modified RECIST v1.1 Criteria
timeFrame: approximately 2 year
measure: Overall Survival (OS)
timeFrame: approximately 2 year
measure: Number of Participants With Adverse Events
timeFrame: approximately 2 year
measure: Maximum Observed Serum Concentration (Cmax) of MEHD7945A
timeFrame: 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)
measure: Minimum Observed Serum Concentration (Cmin) of MEHD7945A
timeFrame: Pre-dose on Day 1 Cycles 1-4, Cycle 8 and at treatment completion (up to approximately 2 year)
Other outcomes:
Locations:
city: Bakersfield
country: United States
state: California
city: Fullerton
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Santa Barbara
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Orange Park
country: United States
state: Florida
city: Harvey
country: United States
state: Illinois
city: Paducah
country: United States
state: Kentucky
city: Rockville
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Jefferson City
country: United States
state: Missouri
city: Las Vegas
country: United States
state: Nevada
city: Philadelphia
country: United States
state: Pennsylvania
city: Kirkland
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Darlinghurst
country: Australia
state: New South Wales
city: New Lambton Heights
country: Australia
state: New South Wales
city: St. Leonards
country: Australia
state: New South Wales
city: Sydney
country: Australia
state: New South Wales
city: Waratah
country: Australia
state: New South Wales
city: Wollongong
country: Australia
state: New South Wales
city: Herston
country: Australia
state: Queensland
city: Southport
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Frankston
country: Australia
state: Victoria
city: Bruxelles
country: Belgium
city: Charleroi
country: Belgium
city: Haine-Saint-Paul
country: Belgium
city: Leuven
country: Belgium
city: Liège
country: Belgium
city: Creteil
country: France
city: Lyon
country: France
city: Paris
country: France
city: Villejuif
country: France
city: Dresden
country: Germany
city: München
country: Germany
city: München
country: Germany
city: Stuttgart
country: Germany
city: Trier
country: Germany
city: Milano
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Orbassano
country: Italy
state: Piemonte
city: Pisa
country: Italy
state: Toscana
city: Padova
country: Italy
state: Veneto
city: Auckland
country: New Zealand
city: Christchurch
country: New Zealand
city: Dunedin
country: New Zealand
city: Tauranga
country: New Zealand
city: Brasov
country: Romania
city: Bucharest
country: Romania
city: Bucuresti
country: Romania
city: Iasi
country: Romania
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Valencia
country: Spain
city: Aberdeen
country: United Kingdom
city: London
country: United Kingdom
city: Oxford
country: United Kingdom
city: Wirral
country: United Kingdom
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
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.