A Randomized, Double-blind, Placebo-controlled Phase III Study of Regorafenib Plus BSC Versus Placebo Plus BSC in Patients With Metastatic Colorectal Cancer (CRC) Who Have Progressed After Standard Therapy
Overview
- Phase
- Phase 3
- Intervention
- Regorafenib (Stivarga, BAY73-4506)
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Bayer
- Enrollment
- 760
- Primary Endpoint
- Overall Survival
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This is a randomized, double-blind, placebo-controlled multi-center phase III study to evaluate efficacy and safety of regorafenib in patients with metastatic colorectal cancer (CRC) who have progressed on/after all approved drugs for CRC
Detailed Description
All participants received Best Supportive Care. Acronyms used in Adverse events section: Gastrointestinal (GI), Genitourinary (GU), Not Otherwise Specified (NOS), Absolute Neutrophil Count (ANC), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Common Terminology Criteria for Adverse Events (CTCAE), International Normalized Ratio (INR), Central nervous system (CNS), Acute respiratory distress syndrome (ARDS), Cranial nerves (CN), Disseminated Intravascular Coagulation (DIC), Cardiac troponin T (cTnT). Abbreviation used in Results section: Data Monitoring Committee (DMC). Adverse event collection will be covered in Adverse events section.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histological or cytological documentation of adenocarcinoma of the colon or rectum
- •Progression during or within 3 months following the last administration of approved standard therapies. Patients treated with oxaliplatin in an adjuvant setting should have progressed during or within 6 months of completion of adjuvant therapy
- •Patients with measurable or non measurable disease
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of \</= 1
- •Life expectancy of at least 3 months
- •Adequate bone marrow, liver and renal function
Exclusion Criteria
- •Unstable/uncontrolled cardiac disease
- •History of arterial or venous thrombotic or embolic events
- •Symptomatic metastatic brain or meningeal tumors
- •Patients with evidence or history of bleeding diathesis
- •Interstitial lung disease - Persistent proteinuria \>/= grade 3
- •Unresolved toxicity \> grade 1 attributed to any prior therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity \</= Grade 2
Arms & Interventions
Regorafenib (Stivarga, BAY73-4506)+BSC
Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care(BSC).
Intervention: Regorafenib (Stivarga, BAY73-4506)
Regorafenib (Stivarga, BAY73-4506)+BSC
Participants received Regorafenib 160 mg per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care(BSC).
Intervention: Best Supportive Care (BSC)
Placebo+BSC
Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care (BSC).
Intervention: Placebo
Placebo+BSC
Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle plus Best Supportive Care (BSC).
Intervention: Best Supportive Care (BSC)
Outcomes
Primary Outcomes
Overall Survival
Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis (IA).
Overall survival (OS) was defined as the time (days) from randomization to death due to any cause. Patients alive at the time of analysis were censored at the last date known to be alive. If a patient was lost to follow-up and there was no contact after randomization, this patient was censored at Day 1.
Secondary Outcomes
- Progression-free Survival (Based on Investigator's Assessment)(From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.)
- Objective Tumor Response(From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.)
- Disease Control(From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.)
- Tumor Response(From randomization of the first subject until the database cut-off approximately 14 months later (19May2010 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals.)