First Line Treatment of Metastatic Colorectal Cancer With mFOLFOX6 in Combination With Regorafenib - Full Text View

Purpose

This is a study to evaluate the efficacy (effectiveness) and the safety of regorafenib when given in combination with chemotherapy mFOLFOX6 as first line therapy in patients with metastatic colorectal cancer (CRC). mFOLFOX6 is an approved chemotherapy. Regorafenib is an oral (i.e. taken by mouth) multi-targeted kinase inhibitor. A kinase inhibitor targets certain key proteins that are essential for the survival of the cancer cell. By specifically targeting these proteins, regorafenib may stop cancer growth. The growth of the tumor may be decreased by preventing these specific proteins from functioning.

The primary endpoint (the most meaningful result to be tracked) of this study is based on the rate of response, i.e. the disease getting smaller. The aim is to show that the therapy of colorectal cancer with mFOLFOX6 in combination with regorafenib improves the response rate observed for the standard therapy only.

Condition	Intervention	Phase
Colorectal Neoplasms	Drug: Regorafenib (Stivarga, BAY73-4506)	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Uncontrolled, Open-label, Phase II Study in Subjects With Metastatic Adenocarcinoma of the Colon or Rectum Who Are Receiving First Line Chemotherapy With mFOLFOX6 (Oxaliplatin/ Folinic Acid/5-fluorouracil [5-FU]) in Combination With Regorafenib

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Folic acid Leucovorin calcium Levoleucovorin Regorafenib

U.S. FDA Resources

Further study details as provided by Bayer:

Primary Outcome Measures:

Objective response rate [ Time Frame: 6 months after last patient first treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Time Frame: 3 months after last patient last visit ] [ Designated as safety issue: No ]
Progression-free survival [ Time Frame: 3 months after last patient last visit ] [ Designated as safety issue: No ]
Disease control rate [ Time Frame: 3 months after last patient last visit ] [ Designated as safety issue: No ]
Duration of response [ Time Frame: 3 months after last patient last visit ] [ Designated as safety issue: No ]
Duration of stable disease [ Time Frame: 3 months after last patient last visit ] [ Designated as safety issue: No ]

Enrollment:	54
Study Start Date:	February 2011
Estimated Study Completion Date:	October 2013
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Regorafenib	Drug: Regorafenib (Stivarga, BAY73-4506) On day 1 and day 15 of each cycle, subjects will receive 85 mg/m² oxaliplatin and folinic acid (either 400 mg/m² D/L-folinic acid or 200 mg/m² L-folinic acid) as a 2 hour i.v. infusion. Once the infusion is done, subjects will receive a 400 mg/m² 5 FU i.v. bolus injection immediately followed by a 2400 mg/m² 5 FU 46 hour i.v. infusion. Subjects will receive regorafenib 160 mg od on days 4 to 10 and days 18 to 24 as four 40 mg coprecipitate tablets. In case of administration as a single agent during the study, regorafenib will be administered 160 mg od for 3 weeks on/1 week off. Each cycle consists of 28 days.

Arms

Assigned Interventions

Experimental: Regorafenib

Drug: Regorafenib (Stivarga, BAY73-4506)

On day 1 and day 15 of each cycle, subjects will receive 85 mg/m² oxaliplatin and folinic acid (either 400 mg/m² D/L-folinic acid or 200 mg/m² L-folinic acid) as a 2 hour i.v. infusion. Once the infusion is done, subjects will receive a 400 mg/m² 5 FU i.v. bolus injection immediately followed by a 2400 mg/m² 5 FU 46 hour i.v. infusion. Subjects will receive regorafenib 160 mg od on days 4 to 10 and days 18 to 24 as four 40 mg coprecipitate tablets. In case of administration as a single agent during the study, regorafenib will be administered 160 mg od for 3 weeks on/1 week off. Each cycle consists of 28 days.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female subjects aged ≥ 18 years
Histological or cytological documentation of adenocarcinoma of the colon or rectum
Suitable to receive mFOLFOX6 regimen as first line metastatic treatment
At least 1 measurable lesion as per RECIST version 1.1
Unresectable or unlikely becoming resectable metastatic disease
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Life expectancy of at least 3 months
Adequate bone marrow, liver, and renal function

Exclusion Criteria:

Prior systemic anticancer therapy for metastatic colorectal cancer (CRC). Adjuvant chemotherapy for CRC (Stage I, II, III) is permitted, if the adjuvant therapy ended > 6 months before screening and recurrent disease was documented.
Prior treatment with antivascular endothelial growth factor (anti-VEGF) agents and any signal transduction inhibitors (STIs)
Uncontrolled hypertension
Subjects with symptoms, signs, or history of brain metastases
Any hemorrhage or bleeding event ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 within 4 weeks of start of study treatment
Sensory neuropathy (> CTCAE Grade 1), unresolved toxicity > CTCAE Grade 1 attributed to any prior therapy/procedure excluding alopecia

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289821

Locations

United States, Illinois

Chicago, Illinois, United States, 60611-2906
Australia, New South Wales

Concord, New South Wales, Australia, 2139
Australia, South Australia

Woodville South, South Australia, Australia, 5011
Belgium

Bruxelles - Brussel, Belgium, 1070

Edegem, Belgium, 2650

Leuven, Belgium, 3000
Germany

Stuttgart, Baden-Württemberg, Germany, 70199

Oldenburg, Niedersachsen, Germany, 26133

Herne, Nordrhein-Westfalen, Germany, 44625

Dresden, Sachsen, Germany, 01307
Italy

Ancona, Italy, 60020

Genova, Italy, 16132

Napoli, Italy, 80131
Spain

Santander, Cantabria, Spain, 39008

Barcelona, Spain, 08035

Madrid, Spain, 28034
United Kingdom

Glasgow, United Kingdom, G12 0YN

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Bayer

Investigators

Study Director:

Bayer Study Director

Bayer

More Information

Additional Information:

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No publications provided

Responsible Party:	Therapeutic Area Head, Bayer Healthcare Pharmaceuticals Inc.
ClinicalTrials.gov Identifier:	NCT01289821 History of Changes
Other Study ID Numbers:	11728, 2010-020121-41
Study First Received:	February 3, 2011
Last Updated:	December 14, 2012
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Germany: Federal Institute for Drugs and Medical Devices Italy: The Italian Medicines Agency Spain: Ministry of Health and Consumption United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration

Additional relevant MeSH terms:

Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases

Intestinal Diseases
Rectal Diseases
Leucovorin
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013