Clinical trial NCT01399684: A Study Evaluating the Efficacy and Safety of MEGF0444A Dosed to Progression in Combination With Bevacizumab and mFOLFOX-6 in Participants With Previously Untreated Metastatic Colorectal Cancer
Official title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of MEGF0444A Dosed to Progression in Combination With Bevacizumab and FOLFOX in Patients With Previously Untreated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-07-22
Enrollment: 127
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 is a Phase II, multicenter, randomized, double-blind, placebo-controlled trial designed to estimate the efficacy of MEGF0444A treatment to disease progression, combined with oxaliplatin + folinic acid + 5-Fluorouracil (mFOLFOX-6) + bevacizumab therapy in participants with metastatic colorectal cancer (CRC).


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed CRC not amenable to potentially curative resection with at least one measurable metastatic lesion, as defined by RECIST v1.1
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate hematologic and end organ function
* For female participants of childbearing potential and male participants with partners of childbearing potential, agreement to use a highly effective form of contraception and to continue its use for 6 months after the last dose of study treatment
* Negative serum pregnancy test within 7 days prior to starting study treatment in premenopausal women and women less than (\<) 2 years after the onset of menopause

Exclusion Criteria:

Disease-specific exclusions

* Any prior systemic therapy (including chemotherapy, antibody therapy, tyrosine kinase inhibitors, radiotherapy, immunotherapy, hormonal therapy or investigational therapy) before Day 1 of Cycle 1 for treatment of CRC General Medical Exclusions
* Malignancies other than CRC within 5 years prior to randomization, except for those with a negligible risk of metastasis or death
* Radiotherapy to any site for any reason within 28 days prior to Day 1 of Cycle 1
* Clinically detectable third-space fluid collections that cannot be controlled by drainage or other procedures prior to study entry
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to Day 1 of Cycle 1
* Lactating women
* Clinically suspected or confirmed central nervous system (CNS) metastases or carcinomatous meningitis
* Active infection requiring IV antibiotics
* Active autoimmune disease that is not controlled by nonsteroidal anti-inflammatory drugs, inhaled corticosteroids, or the equivalent of less than or equal to (\</=) 10 milligrams per day (mg/day) prednisone
* Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, or cirrhosis
* Sensory peripheral neuropathy greater than or equal to (\>/=) Grade 2 Bevacizumab-Specific Exclusions
* Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of bevacizumab or an investigational drug or that may affect the interpretation of the results or render the participant at high risk for treatment complications
* Inadequately controlled hypertension
* Prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Class II or greater congestive heart failure (CHF)
* History of myocardial infarction or unstable angina within 6 months prior to Day 1
* History of stroke or transient ischemic attack (TIA) within 6 months prior to Day 1
* Significant vascular disease within 6 months prior to Day 1
* Evidence of bleeding diathesis or significant coagulopathy
* Current or recent (within 10 days of first dose of study treatment) use of aspirin or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol
* Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
* History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI) perforation within 6 months prior to Day 1
* Clinical signs or symptoms of GI obstruction or a requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
* Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
* Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture 5-Fluorouracil-Specific Exclusion
* Known dihydropyrimidine dehydrogenase deficiency or thymidylate synthase gene polymorphism predisposing the participant for 5-fluorouracil toxicity

Primary outcomes:
measure: Progression-Free Survival Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator
timeFrame: Screening up to disease progression or death due to any cause, whichever occurs first (assessed every 8-9 weeks after Cycle 1 Day 1 up to approximately 27 months overall)
Secondary outcomes:
measure: Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR] Based on RECIST v 1.1 as Determined by the Investigator
timeFrame: Screening up to disease progression or death due to any cause, whichever occurs first (assessed every 8 -9 weeks after Cycle 1 Day 1 up to approximately 27 months overall)
measure: Duration of Response Based on RECIST v 1.1 as Determined by the Investigator
timeFrame: Screening up to disease progression or death due to any cause, whichever occurs first (assessed every 8 -9 weeks after Cycle 1 Day 1 up to approximately 27 months overall)
measure: Overall Survival (OS)
timeFrame: Screening until death (up to approximately 27 months overall)
measure: Percentage of Participants with Adverse Events
timeFrame: Up to approximately 27 months overall
measure: Maximum Serum Concentration (Cmax) of MEGF0444A
timeFrame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2; prior to first infusion on Day 1 of Cycles 3 and 8; at study drug discontinuation visit (up to 24 months)
measure: Minimum Serum Concentration (Cmin) of MEGF0444A
timeFrame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2; prior to first infusion on Day 1 of Cycles 3 and 8; at study drug discontinuation visit (up to 24 months)
measure: Cmax of Bevacizumab
timeFrame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2
measure: Cmin of Bevacizumab
timeFrame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2
measure: Plasma Concentration of 5-Fluorouracil
timeFrame: Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of 5-fluorouracil bolus, 2 hours after end of 5-fluorouracil bolus, 12-24 hours after end of 5-fluorouracil bolus on Day 1 of Cycles 1, 2
measure: Plasma Concentration of Oxaliplatin
timeFrame: Prior to the first infusion (first infusion being MEGF0444A administration), 5-10 minutes before end of oxaliplatin infusion, 2 hours after end of 5-fluorouracil bolus, 12-24 hours after end of 5-fluorouracil bolus on Day 1 of Cycles 1, 2
measure: Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to MEGF0444A
timeFrame: Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 3 and 8, (cycle length = 14 days), at study drug discontinuation visit (up to 24 months)
measure: Change From Baseline in ATAs Levels of MEGF0444A
timeFrame: Pre-dose (within 1 hour before infusion start) on Day 1 of Cycles 1, 3 and 8, (cycle length = 14 days), at study drug discontinuation visit (up to 24 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
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: Pasadena
country: United States
state: California
city: San Luis Obispo
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Jacksonville
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Port Saint Lucie
country: United States
state: Florida
city: Lawrenceville
country: United States
state: Georgia
city: Marietta
country: United States
state: Georgia
city: Harvey
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Rochester
country: United States
state: Minnesota
city: Las Vegas
country: United States
state: Nevada
city: Durham
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: South Brisbane
country: Australia
state: Queensland
city: Woodville South
country: Australia
state: South Australia
city: Footscray
country: Australia
state: Victoria
city: Heidelberg
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Bruxelles
country: Belgium
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Gdansk
country: Poland
city: Krakow
country: Poland
city: Poznan
country: Poland
city: Warszawa
country: Poland
city: Santander
country: Spain
state: Cantabria
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
Study officials:
affiliation: Genentech, Inc.
name: Ina Rhee, M.D., Ph.D.
role: STUDY_DIRECTOR
References:
citation: Garcia-Carbonero R, van Cutsem E, Rivera F, Jassem J, Gore I Jr, Tebbutt N, Braiteh F, Argiles G, Wainberg ZA, Funke R, Anderson M, McCall B, Stroh M, Wakshull E, Hegde P, Ye W, Chen D, Chang I, Rhee I, Hurwitz H. Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with FOLFOX and Bevacizumab for First-Line Metastatic Colorectal Cancer. Oncologist. 2017 Apr;22(4):375-e30. doi: 10.1634/theoncologist.2016-0133. Epub 2017 Mar 8.