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

Metastatic Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01103323
• Other study ID #: 14387
• Secondary ID: 2009-012787-14
• Status: Completed
• Phase: Phase 3
• First received: April 8, 2010
• Last updated: May 28, 2015
• Start date: April 2010
• Est. completion date: January 2014

Study information

• Verified date: May 2015
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: National Institute of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyCzech Republic: State Institute for Drug ControlHungary: National Institute of PharmacyAustralia: Department of Health and Ageing Therapeutic Goods AdministrationChina: Food and Drug AdministrationJapan: Pharmaceuticals and Medical Devices AgencyBrazil: National Health Surveillance AgencyArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaSwitzerland: SwissmedicCanada: Health CanadaSpain: Spanish Agency of MedicinesPortugal: National Pharmacy and Medicines InstituteTurkey: Ministry of HealthIsrael: Ministry of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Belgium: Federal Agency for Medicinal Products and Health ProductsUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 760
• Est. completion date: January 2014
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

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)
• Placebo
matching placebo tablets for 3 weeks of every 4 week cycle (i.e., 3 weeks on, 1 week off)

Other:
• Best Supportive Care (BSC)
BSC includes any concomitant medications or treatments: antibiotics, analgesics, radiation therapy for pain control (limited to bone metastases), corticosteroids, transfusions, psychotherapy, growth factors, palliative surgery, or any other symptomatic therapy necessary to provide BSC, except other investigational anti-tumor agents or anti-neoplastic chemo/hormonal/immuno-therapy.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czech Republic,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Netherlands,  Portugal,  Spain,  Switzerland,  Turkey, 

References & Publications (2)

Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monothera — View Citation

Mross K, Frost A, Steinbild S, Hedbom S, Büchert M, Fasol U, Unger C, Krätzschmar J, Heinig R, Boix O, Christensen O. A phase I dose-escalation study of regorafenib (BAY 73-4506), an inhibitor of oncogenic, angiogenic, and stromal kinases, in patients wit — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	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.	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).	No
Secondary	Progression-free Survival (Based on Investigator's Assessment)	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.	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.	No
Secondary	Objective Tumor Response	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.	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.	No
Secondary	Disease Control	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.	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.	No
Secondary	Tumor Response	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.	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.	No

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