Patients With Metastatic Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy

Phase 3

Completed

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Placebo; Drug: Regorafenib (Stivarga, BAY73-4506); Other: Best Supportive Care (BSC)

• Registration Number: NCT01103323
• Lead Sponsor: Bayer

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.

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-04-08
• Study First Submitted QC: 2010-04-13
• Study First Posted: 2010-04-14
• Primary Completion: 2011-07
• Results First Submitted: 2012-10-19
• Results First Submitted QC: 2012-10-19
• Results First Posted: 2012-11-19
• Study Completion: 2014-01
• Status Verified: 2015-05
• Last Update Submitted: 2015-05-28
• Last Update Posted: 2015-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 760

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regorafenib (Stivarga, BAY73-4506)+BSC	Best Supportive Care (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).
Placebo+BSC	Placebo	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).
Regorafenib (Stivarga, BAY73-4506)+BSC	Regorafenib (Stivarga, BAY73-4506)	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).
Placebo+BSC	Best Supportive Care (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).

Primary Outcome Measures

Name	Time	Method
Overall Survival	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 Outcome Measures

Name	Time	Method
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.	Progression-free survival was defined as the time (days) from date of randomization to date of first observed disease progression (radiological or clinical) or death due to any cause, if death occurred before progression was documented.
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.	The objective tumor response was defined as the percentage of patients with complete response (CR, tumor disappears) or partial response (PR, sum of lesion sizes decreased at least 30% from baseline) as best overall response. A best overall response was defined for all patients, using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. Patients whose best overall response was not CR or PR, and any patients with no post-baseline assessments were considered nonresponders for the analysis.
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.	Disease control was defined as the percentage of patients whose best response was not PD \[sum of lesion sizes increased at least 20% from smallest sum on study or new lesions\] (ie, CR \[tumor disappears\], PR \[sum of lesion sizes decreased at least 30% from baseline\] or SD (stable disease)). SD included if at least 6 weeks after randomization.
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.	A tumor response (best overall response) was defined for all patients, using the RECIST criteria, version 1.1. Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased at least 30% from baseline), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased at least 20% from smallest sum on study or new lesions). Clinical PD considered when radiographic imaging not possible.