First Line Treatment of Metastatic Colorectal Cancer With mFOLFOX6 in Combination With Regorafenib
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.
Drug: Regorafenib (Stivarga, BAY73-4506)
Drug: Folinic acid
Drug: 5-FU (mFOLFOX6)
|Study Design:||Allocation: Non-Randomized
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|
- Objective Response (OR) [ Time Frame: From start of treatment until 30 days after termination of study medication, an average of 47 weeks. Assessed every 8 weeks. ]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.
- Overall Survival (OS) [ Time Frame: From start of treatment of first participant until database cut-off approximately 13 months later (7 FEB 2011 - 5 MAR 2012). Assessed every 8 weeks. ]OS was calculated as the time from first date of receiving study treatment to date of death due to any cause. Participants alive at the time of analysis were censored at their last date of follow-up.
- Progression-free Survival (PFS) [ Time Frame: From start of treatment of the first participant until database cut-off approximately 13 months later (7 FEB 2011 - 5 MAR 2012). Assessed every 8 weeks. ]PFS was defined as time from the date of start of study treatment to the date of first observed disease progression (radiological according to central assessment or clinical), or death due to any cause, if death occurred before progression was documented. PFS for participants without disease progression or death at the date of database cutoff were right-censored at the last date of tumor assessment. Participants who had no tumor evaluation after baseline and no clinical progression post baseline and who did not die were censored at Day 1 in the analysis. PD = At least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non target lesions or the appearance of one or more new lesions will also constitute PD.
- Disease Control (DC) [ Time Frame: From start of treatmentof the first participant until database cut-off approximately 13 months later (7 FEB 2011 - 5 MAR 2012). Assessed every 8 weeks. ]DC was defined as the proportion of participants who had a best response rating of CR, PR, or stable disease (SD) according to RECIST criteria that was achieved during treatment or within 30 days after termination of study treatment. CR and PR were confirmed not earlier than 4 weeks following the initial detection of response. A minimum of 8 weeks (allowing a minus 7-day time window) between start of study treatment and the first follow-up tumor assessment with SD as response was required to assign SD as best overall response.
- Duration of Response (DOR) [ Time Frame: From start of treatment of first participant until database cut-off approximately 13 months later (7 FEB 2011 - 5 MAR 2012). Assessed every 8 weeks. ]DOR was defined as the time from the date of first documented objective response of PR or CR, whichever was noted earlier, to first subsequent disease progression or death (if death occurred before progression was documented). DOR was defined for responders only (that is, subjects with CR or PR). DOR for subjects without disease progression or death before progression was right censored at the date of their last tumor assessment.
- Duration of Stable Disease (DOSD) [ Time Frame: From start of treatment of first participant until database cut-off approximately 13 months later (7 FEB 2011 - 5 MAR 2012). Assessed every 8 weeks. ]DOSD was only evaluated in participants failing to achieve a best response of CR or PR, but who achieved SD. DOSR was defined as the time (in days) from date of start of study treatment to the date at which disease progression or death (if death occurred before progression was first documented). The date the tumor scan was performed was used for this calculation. DOSD for participants without disease progression or death before progression at the time of analysis were censored at the date of their last tumor assessment.
|Study Start Date:||February 2011|
|Study Completion Date:||June 2014|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: Regorafenib + oxaliplatin/folinic acid/5-FU (mFOLFOX6)
On Day 1, participants received 85 mg/m2 oxaliplatin as a 2-hour intravenous (IV) infusion and folinic acid (either 400 mg/m2 D/L‑folinic acid or 200 mg/m2 L-folinic acid) as a 2-hour IV infusion. Once the initial infusion was completed, participants received 5-FU 400 mg/m2 IV bolus injection immediately followed by a 5-FU 2400 mg/m2 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)
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.Drug: Oxaliplatin
On day 1 and day 15 of each cycle, participants will receive 85 mg/m² oxaliplatin as a 2 hour i.v. infusion.Drug: Folinic acid
On day 1 and day 15 of each cycle, participants will receive folinic acid (either 400 mg/m² D/L-folinic acid or 200 mg/m² L-folinic acid) as a 2 hour i.v. infusion.Drug: 5-FU (mFOLFOX6)
Participants 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01289821
|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|
|Bruxelles - Brussel, Belgium, 1070|
|Edegem, Belgium, 2650|
|Leuven, Belgium, 3000|
|Stuttgart, Baden-Württemberg, Germany, 70199|
|Oldenburg, Niedersachsen, Germany, 26133|
|Herne, Nordrhein-Westfalen, Germany, 44625|
|Dresden, Sachsen, Germany, 01307|
|Ancona, Italy, 60126|
|Genova, Italy, 16132|
|Napoli, Italy, 80131|
|Santander, Cantabria, Spain, 39008|
|Barcelona, Spain, 08035|
|Madrid, Spain, 28034|
|Glasgow, United Kingdom, G12 0YN|
|Manchester, United Kingdom, M20 4BX|
|Study Director:||Bayer Study Director||Bayer|