Clinical trial NCT01374425: Study of Bevacizumab + mFOLFOX6 Versus Bevacizumab + FOLFIRI With Biomarker Stratification in Participants With Previously Untreated Metastatic Colorectal Cancer (mCRC)
Official title: MAVERICC (Marker Evaluation for Avastin Research in CRC): A Randomized Phase II Study of Bevacizumab+mFOLFOX6 Vs. Bevacizumab+FOLFIRI With Biomarker Stratification in Patients With Previously Untreated Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-06-16
Enrollment: 376
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 will be a randomized, open-label, multicenter, Phase II study with primary objectives to assess whether expression of select chemotherapy markers is associated with progression-free survival (PFS) in participants treated with bevacizumab plus leucovorin, 5-fluorouracil, and oxaliplatin (mFOLFOX6) or bevacizumab plus leucovorin, 5-fluorouracil, and irinotecan (FOLFIRI). The study population will consist of participants with first-line mCRC.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed colorectal cancer (CRC) with at least one measurable metastatic lesion by RECIST Version 1.1
* Archival tumor tissue sample must be requested and available prior to study entry. If no archival tumor tissue sample is available, a fresh biopsy tissue sample must be obtained but should be discussed first with the medical monitor. A copy of the local pathology report must be submitted along with the specimens.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants with treated brain metastases are eligible for study participation. Participants may not receive ongoing treatment with steroids at Screening. Anticonvulsants (at stable dose) are allowed. Treatment for brain metastases may be whole-brain radiotherapy, radiosurgery, neurosurgery, or a combination as deemed appropriate by the treating physician. Radiotherapy and stereotactic radiosurgery must be completed at least 28 days prior to randomization.
* Female participants should not be pregnant or breastfeeding. Female participants with childbearing potential should agree to use effective, non-hormonal means of contraception during the study and for a period of at least 6 months following the last administration of study drugs. Female participants with an intact uterus (unless amenorrheic for the last 24 months) must have a negative serum pregnancy test within 7 days prior to randomization into the study.
* Male participants must agree to use effective contraception during the study and for a period of at least 6 months following the last administration of study drugs, even if they have been surgically sterilized.

Exclusion Criteria:

* Any prior systemic treatment for mCRC
* Adjuvant chemotherapy for CRC completed \<12 months
* Evidence of Gilbert's syndrome or of homozygosity for the UGT1A1\*28 allele
* Known positivity for human immunodeficiency virus (HIV)
* Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent
* Radiotherapy to any site for any reason within 28 days prior to randomization, except for palliative radiotherapy to bone lesions within 14 days prior to randomization
* 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 investigational drug trial within 28 days prior to randomization

Primary outcomes:
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With High Vascular Endothelial Growth Factor (VEGF)-A Levels Versus Participants With Low VEGF-A Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
Secondary outcomes:
measure: PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and High VEGF-A Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With High ERCC-1 and Low VEGF-A Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and High VEGF-A Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With Low ERCC-1 and Low VEGF-A Levels
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Overall Survival (OS)
timeFrame: From Baseline until death (maximum up to 45 months overall)
measure: OS in Participants With High ERCC-1 Levels
timeFrame: From Baseline until death (maximum up to 45 months overall)
measure: OS in Participants With Low ERCC-1 Levels
timeFrame: From Baseline until death (maximum up to 45 months overall)
measure: OS in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
timeFrame: From Baseline until death (maximum up to 45 months overall)
measure: Percentage of Participants With Objective Response According to RECIST Version 1.1
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Disease Control According to RECIST Version 1.1
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With Low ERCC-1 Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Liver Metastasis Resection
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Complete Liver Metastasis Resection
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Liver Metastasis Resection in Participants With Low ERCC-1 Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Complete Liver Metastasis Resection in Participants With Low ERCC-1 Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Complete Liver Metastasis Resection in Participants With High ERCC-1 Levels Versus Participants With Low ERCC-1 Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: PFS According to RECIST Version 1.1 in Participants With Wild-Type V-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Versus Participants With Mutant KRAS
timeFrame: From Baseline until death or disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: OS in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
timeFrame: From Baseline until death (maximum up to 45 months overall)
measure: OS in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS
timeFrame: From Baseline until death (maximum up to 45 months overall)
measure: Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Objective Response According to RECIST Version 1.1 in Participants With Wild-Type KRAS Versus Participants With Mutant KRAS
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Disease Control According to RECIST Version 1.1 in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
timeFrame: From Baseline until disease progression; assessed every 6 weeks (maximum up to 45 months overall)
measure: Percentage of Participants With Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
measure: Percentage of Participants With Complete Liver Metastasis Resection in Participants With High VEGF-A Levels Versus Participants With Low VEGF-A Levels
timeFrame: At time of resective surgery during study (maximum up to 45 months overall)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Little Rock
country: United States
state: Arkansas
city: Bellflower
country: United States
state: California
city: Duarte
country: United States
state: California
city: Fountain Valley
country: United States
state: California
city: Fresno
country: United States
state: California
city: Hayward
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Oakland
country: United States
state: California
city: Pleasant Hill
country: United States
state: California
city: Roseville
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Jose
country: United States
state: California
city: Santa Clara
country: United States
state: California
city: South San Francisco
country: United States
state: California
city: Vallejo
country: United States
state: California
city: Walnut Creek
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Stamford
country: United States
state: Connecticut
city: Trumbull
country: United States
state: Connecticut
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Port Saint Lucie
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Joliet
country: United States
state: Illinois
city: Maywood
country: United States
state: Illinois
city: Peoria
country: United States
state: Illinois
city: Goshen
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Terre Haute
country: United States
state: Indiana
city: Fairway
country: United States
state: Kansas
city: Elizabethtown
country: United States
state: Kentucky
city: Scarborough
country: United States
state: Maine
city: Burlington
country: United States
state: Massachusetts
city: Billings
country: United States
state: Montana
city: Lincoln
country: United States
state: Nebraska
city: Cherry Hill
country: United States
state: New Jersey
city: Manasquan
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Albuquerque
country: United States
state: New Mexico
city: Albuquerque
country: United States
state: New Mexico
city: Farmington
country: United States
state: New Mexico
city: Las Cruces
country: United States
state: New Mexico
city: Santa Fe
country: United States
state: New Mexico
city: Rochester
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Greensboro
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Washington
country: United States
state: North Carolina
city: Winston-salem
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Dunmore
country: United States
state: Pennsylvania
city: Media
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Corpus Christi
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
city: Wauwatosa
country: United States
state: Wisconsin
city: Edmonton
country: Canada
state: Alberta
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Cork
country: Ireland
city: Dublin
country: Ireland
city: Galway
country: Ireland
city: Oslo
country: Norway
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Aarau
country: Switzerland
city: Basel
country: Switzerland
city: Luzern
country: Switzerland
city: Zürich
country: Switzerland
Study officials:
affiliation: Genentech, Inc.
name: Christiane Langer, M.D.
role: STUDY_DIRECTOR
References: