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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01399684




Registration number
NCT01399684
Ethics application status
Date submitted
20/07/2011
Date registered
22/07/2011
Date last updated
26/08/2016

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
GO27812
Secondary ID [2] 0 0
MEF4982g
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 5-Fluorouracil
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Folinic acid
Treatment: Drugs - MEGF0444A
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Placebo

Experimental: MEGF0444A + mFOLFOX-6 + Bevacizumab - Participants will receive MEGF0444A + mFOLFOX-6 (oxaliplatin, folinic acid, and 5-fluorouracil) regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles (Cycle = 14 days) and 5-fluorouracil, folinic acid, bevacizumab and MEGF0444A will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.

Placebo comparator: Placebo + mFOLFOX-6 + Bevacizumab - Participants will receive MEGF0444A matching placebo + mFOLFOX-6 regimen + bevacizumab. Participants will receive oxaliplatin for up to 8 cycles and 5-fluorouracil, folinic acid, bevacizumab and placebo will be administered until disease progression or unacceptable toxicity for a maximum of up to 52 cycles.


Treatment: Drugs: 5-Fluorouracil
Participants will receive 5-fluorouracil 400 milligrams per squared meter (mg/m\^2) intravenous (IV) bolus and then 2400 mg/m\^2 as a continuous IV infusion over 46-48 hours on Day 1 of every cycle until disease progression, unacceptable toxicity or at the maximum of 52 cycles, whichever occurs first.

Treatment: Drugs: Bevacizumab
Participants will be administered bevacizumab at a dose of 5 milligrams per kilogram (mg/kg) every 14 days until disease progression or unacceptable toxicity, for a maximum of 52 cycles, whichever occurs first.

Treatment: Drugs: Folinic acid
Participants will receive folinic acid 400 mg/m\^2 IV infusion over 2 hours on Day 1 of every cycle until disease progression, unacceptable toxicity or at the maximum of 52 cycles, whichever occurs first.

Treatment: Drugs: MEGF0444A
Participants will be administered MEGF0444A at a fixed dose of 400 milligrams (mg) IV on Day 1 of Cycle 1, followed by subsequent doses of 400 mg every 14 days until disease progression or unacceptable toxicity, for a maximum of 52 cycles, whichever occurs first.

Treatment: Drugs: Oxaliplatin
Participants will receive oxaliplatin 85 mg/m\^2 IV infusion over 90 minutes on Day 1 of every cycle for a maximum of 8 cycles.

Treatment: Drugs: Placebo
Participants will be administered MEGF0444A matching placebo every 14 days until disease progression, unacceptable toxicity or at the maximum of 52 cycles, whichever occurs first.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 as Determined by the Investigator
Timepoint [1] 0 0
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 outcome [1] 0 0
Percentage of Participants with Objective Response (Complete Response [CR] or Partial Response [PR] Based on RECIST v 1.1 as Determined by the Investigator
Timepoint [1] 0 0
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 outcome [2] 0 0
Duration of Response Based on RECIST v 1.1 as Determined by the Investigator
Timepoint [2] 0 0
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 outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Screening until death (up to approximately 27 months overall)
Secondary outcome [4] 0 0
Percentage of Participants with Adverse Events
Timepoint [4] 0 0
Up to approximately 27 months overall
Secondary outcome [5] 0 0
Maximum Serum Concentration (Cmax) of MEGF0444A
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
Minimum Serum Concentration (Cmin) of MEGF0444A
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Cmax of Bevacizumab
Timepoint [7] 0 0
Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2
Secondary outcome [8] 0 0
Cmin of Bevacizumab
Timepoint [8] 0 0
Prior to the first infusion (first infusion being MEGF0444A administration), immediately after end of bevacizumab infusion on Day 1 of Cycles 1, 2
Secondary outcome [9] 0 0
Plasma Concentration of 5-Fluorouracil
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Plasma Concentration of Oxaliplatin
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to MEGF0444A
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
Change From Baseline in ATAs Levels of MEGF0444A
Timepoint [12] 0 0
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)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2014
Sample size
Target
Accrual to date
Final
127
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
- South Brisbane
Recruitment hospital [2] 0 0
- Woodville South
Recruitment hospital [3] 0 0
- Footscray
Recruitment hospital [4] 0 0
- Heidelberg
Recruitment hospital [5] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
5011 - Woodville South
Recruitment postcode(s) [3] 0 0
3011 - Footscray
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Minnesota
Country [12] 0 0
United States of America
State/province [12] 0 0
Nevada
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Leuven
Country [17] 0 0
Poland
State/province [17] 0 0
Gdansk
Country [18] 0 0
Poland
State/province [18] 0 0
Krakow
Country [19] 0 0
Poland
State/province [19] 0 0
Poznan
Country [20] 0 0
Poland
State/province [20] 0 0
Warszawa
Country [21] 0 0
Spain
State/province [21] 0 0
Cantabria
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Sevilla
Country [24] 0 0
Spain
State/province [24] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Ina Rhee, M.D., Ph.D.
Address 0 0
Genentech, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01399684