Study Stopped
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Combination Chemotherapy and Bevacizumab With or Without PRI-724 in Treating Patients With Newly Diagnosed Metastatic Colorectal Cancer
PRIMIER
PRIMIER*: Randomized Phase II Trial of mFOLFOX6/Bevacizumab With or Without PRI-724 as First Line Treatment for Metastatic Colorectal Cancer
4 other identifiers
interventional
N/A
1 country
1
Brief Summary
This randomized phase II trial studies how well combination chemotherapy and bevacizumab with or without CBP/beta-catenin antagonist PRI-724 (PRI-724) works in treating patients with newly diagnosed colorectal cancer that has spread to other places in the body. Drugs used in chemotherapy, such as leucovorin calcium, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may block tumor growth in different ways by targeting certain cells. PRI-724 may help stop the growth of cancer cells by blocking the specific signaling pathway that cancer cells need to grow and spread. It is not yet known whether combination chemotherapy and bevacizumab works better with or without PRI-724 in treating patients with metastatic colorectal cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Nov 2015
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 7, 2015
CompletedFirst Posted
Study publicly available on registry
April 10, 2015
CompletedStudy Start
First participant enrolled
November 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2018
CompletedApril 17, 2017
April 1, 2017
2 years
April 7, 2015
April 13, 2017
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival (PFS)
PFS will be compared between arms by intent-to-treat using Kaplan-Meier curves. The median PFS and 95% confidence interval (CI) will be estimated. Unstratified and stratified hazard ratios and 95% CI will be estimated using the Cox-regression model.
From time of randomization to time of progression or death on study whichever comes first, assessed up to 2 years
Secondary Outcomes (4)
Overall survival (OS)
From time of randomization until death due to any cause, assessed up to 3 years
Overall response rate
Up to 3 years
Incidence of adverse events evaluated according to the National Cancer Institute CTCAE version 4.0
Up to 30 days after the last dose of study drugs
Survivin mRNA expression levels
Up to 3 years
Other Outcomes (2)
KRAS/BRAF mutation status
Baseline
Intratumoral gene expression of Wnt related biomarkers
Up to 3 years
Study Arms (2)
Arm I (PRI-724, mFOLFOX6/bevacizumab)
EXPERIMENTALPatients receive CBP/beta-catenin antagonist PRI-724 IV continuously on days 1-7, bevacizumab IV over 30 minutes, leucovorin calcium IV over 2 hours, oxaliplatin IV over 2 hours, and fluorouracil IV over 46 hours on day 8. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Arm II (mFOLFOX6/bevacizumab)
EXPERIMENTALPatients receive bevacizumab, leucovorin calcium, oxaliplatin, and fluorouracil as in Arm I. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given IV
Given IV
Given IV
Correlative studies
Eligibility Criteria
You may qualify if:
- Histologically confirmed stage IV colorectal adenocarcinoma without any prior systemic treatment
- Signed informed consent prior to initiation of any study-specific procedure or treatment, including consent to provide blood samples for correlative studies and to obtain a tumor biopsy during the study
- Representative tumor tissue specimens (paraffin block preferred)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Able to comply with the protocol, including tissue and blood sampling
- Leukocytes \>= 3,000 per mm\^3
- Absolute neutrophil count \>= 1,500 per mm\^3
- Platelet count \>= 100,000 per mm\^3
- Hemoglobin \>= 9 g/dL (may be transfused to maintain or exceed this level)
- Serum creatinine value \< upper limit of normal (ULN) or creatinine clearance of \>= 60 mL/min according to Cockgroft-Gault formula
- Urine for proteinuria should be \< 2 +; patients discovered to have \>= 2 + proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate \< 1 g of protein in 24 hours
- Serum total bilirubin \< 1.5 mg/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN if there is evidence of hepatic involvement by malignant disease)
- International normalized ratio =\< 1.5 and activated prothrombin time =\< 1.5 x ULN for patients not receiving anti-coagulation therapy
- The use of full-dose oral or parenteral anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits (according to the medical standard of the enrolling institution), and the patient has been on a stable dose of anticoagulants for at least two weeks prior to the first study treatment
- +10 more criteria
You may not qualify if:
- Any prior systemic treatment for metastatic colorectal cancer
- Known hypersensitivity to any of the components of PRI-724, fluorouracil (5-FU), oxaliplatin or bevacizumab
- Adjuvant systemic treatment for colorectal cancer within last 12 months
- Radiotherapy to any site for any reason within 28 days prior to treatment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Sensory peripheral neuropathy \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1
- Corrected QT (QTc) interval \> 470 msec (females) or \> 450 msec (males)
- Active hepatitis B, hepatitis C
- History of arterial thromboembolic events
- History of abdominal fistula formation, gastrointestinal perforation, or abdominal abscess within six months
- History or evidence of inherited bleeding diathesis or coagulopathy with a risk of bleeding
- Patients must not be pregnant or nursing
- Surgery (including open biopsy), significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during study treatment
- Any hemorrhage or bleeding event \>= CTCAE grade 3 within 4 weeks prior to the start of study medication
- Non-healing wound, ulcer, or bone fracture
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Southern Californialead
- National Cancer Institute (NCI)collaborator
- Prism Pharma Co., Ltd.collaborator
Study Sites (1)
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Heinz-Josef Lenz
University of Southern California
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 7, 2015
First Posted
April 10, 2015
Study Start
November 1, 2015
Primary Completion
November 1, 2017
Study Completion
November 1, 2018
Last Updated
April 17, 2017
Record last verified: 2017-04