First Line Treatment of Metastatic Colorectal Cancer With mFOLFOX6 in Combination With Regorafenib

NCT01289821 | Completed Phase 2 Results DMC

• 2 other identifiers: 117282010-020121-41
• Study Type: interventional
• Target: 54
• Locations: 7 countries
• Sites: 18

Brief Summary

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.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Objective Response (OR)

  OR was defined as the best tumor response (confirmed complete response \[CR\] or partial response \[PR\]) observed by MRI or CT scan assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. CR = Disappearance of all clinical and radiological evidence of tumor (both target and no-target). Any pathological lymph nodes (whether target or non target) must have a reduction in short axis to \< 10 mm. PR = At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing nontarget lesions and no appearance of new lesions.

  From start of treatment until 30 days after termination of study medication, an average of 47 weeks. Assessed every 8 weeks.

Secondary Outcomes (5)

• Overall Survival (OS)

  From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks

• Progression-free Survival (PFS)

  From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks

• Disease Control (DC)

  From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks

• Duration of Response (DOR)

  From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks

• Duration of Stable Disease (DOSD)

  From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks

Study Arms (1)

Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)

EXPERIMENTAL

On Day 1, participants received 85 mg/m\^2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m\^2 D/L-folinic acid or 200 mg/m\^2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m\^2 IV bolus injection immediately followed by a 5-FU 2400 mg/m\^2 IV infusion for 46 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17. Participants received Regorafenib (Stivarga, BAY73-4506) 160 mg orally (po) once daily (qd) on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days.

Drug: Regorafenib (Stivarga, BAY73-4506); Drug: Oxaliplatin; Drug: Folinic acid; Drug: 5-FU (mFOLFOX6)

Interventions

Regorafenib (Stivarga, BAY73-4506) DRUG

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.

Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)

Oxaliplatin DRUG

On day 1 and day 15 of each cycle, participants will receive 85 mg/m\^2 oxaliplatin as a 2 hour i.v. infusion.

Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)

Folinic acid DRUG

On day 1 and day 15 of each cycle, participants will receive folinic acid (either 400 mg/m\^2 D/L-folinic acid or 200 mg/m\^2 L-folinic acid) as a 2 hour i.v. infusion.

Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)

5-FU (mFOLFOX6) DRUG

Participants will receive a 400 mg/m\^2 5 FU i.v. bolus injection immediately followed by a 2400 mg/m\^2 5 FU 46 hour i.v. infusion.

Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (18)

Unknown Facility

Chicago, Illinois, 60611-2906, United States

Location

Unknown Facility

Concord, New South Wales, 2139, Australia

Location

Unknown Facility

Woodville South, South Australia, 5011, Australia

Location

Unknown Facility

Bruxelles - Brussel, 1070, Belgium

Location

Unknown Facility

Edegem, 2650, Belgium

Location

Unknown Facility

Leuven, 3000, Belgium

Location

Unknown Facility

Stuttgart, Baden-Wurttemberg, 70199, Germany

Location

Unknown Facility

Oldenburg, Lower Saxony, 26133, Germany

Location

Unknown Facility

Herne, North Rhine-Westphalia, 44625, Germany

Location

Unknown Facility

Dresden, Saxony, 01307, Germany

Location

Unknown Facility

Napoli, Campania, 80131, Italy

Location

Unknown Facility

Genoa, Liguria, 16132, Italy

Location

Unknown Facility

Ancona, The Marches, 60126, Italy

Location

Unknown Facility

Barcelona, Barcelona, 08035, Spain

Location

Unknown Facility

Santander, Cantabria, 39008, Spain

Location

Unknown Facility

Madrid, Madrid, 28034, Spain

Location

Unknown Facility

Manchester, Manchester, M20 4BX, United Kingdom

Location

Unknown Facility

Glasgow, G12 0YN, United Kingdom

Location

Related Publications (1)

• Schultheis B, Folprecht G, Kuhlmann J, Ehrenberg R, Hacker UT, Kohne CH, Kornacker M, Boix O, Lettieri J, Krauss J, Fischer R, Hamann S, Strumberg D, Mross KB. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol. 2013 Jun;24(6):1560-7. doi: 10.1093/annonc/mdt056. Epub 2013 Mar 13.

  PMID: 23493136 RESULT

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayer.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2011
• First Posted: February 4, 2011
• Study Start: February 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: June 1, 2014
• Last Updated: March 15, 2017
• Results First Posted: September 4, 2013

Record last verified: 2017-03

Locations

BE (3); ES (3); GB (2); DE (4); US (1); AU (2); IT (3)