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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT01103323
First received: April 8, 2010
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 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). ] [ Designated as safety issue: No ]
    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:
  • Progression-free Survival (Based on Investigator's Assessment) [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From randomization of the first subject until the database cut-off approximately 14 months later (19May2012 - 21Jul2011) used for 2nd planned formal interim analysis. Tumor assessed at 8 week intervals. ] [ Designated as safety issue: No ]
    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.


Enrollment: 760
Study Start Date: April 2010
Study Completion Date: January 2014
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Regorafenib (Stivarga, BAY73-4506)
160 mg per oral once daily for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off) plus Best Supportive Care
Placebo Comparator: Placebo
Participants received matching placebo tablets per oral once daily for 3 weeks on 1 week off of every 4 week cycle
Drug: Placebo
matching placebo tablets for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off) plus Best Supportive Care

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01103323

  Show 171 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT01103323     History of Changes
Other Study ID Numbers: 14387, 2009-012787-14
Study First Received: April 8, 2010
Results First Received: October 19, 2012
Last Updated: April 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: National Institute of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: State Institute for Drug Control
Hungary: National Institute of Pharmacy
Australia: Department of Health and Ageing Therapeutic Goods Administration
China: Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency
Brazil: National Health Surveillance Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Switzerland: Swissmedic
Canada: Health Canada
Spain: Spanish Agency of Medicines
Portugal: National Pharmacy and Medicines Institute
Turkey: Ministry of Health
Israel: Ministry of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Belgium: Federal Agency for Medicinal Products and Health Products
United States: Food and Drug Administration

Keywords provided by Bayer:
Metastatic Colorectal Cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 20, 2014