Clinical Trial Results:
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
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Summary
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EudraCT number |
2010-020121-41 |
Trial protocol |
GB DE BE ES IT |
Global end of trial date |
30 Jun 2014
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Results information
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Results version number |
v1 |
This version publication date |
12 Jul 2016
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First version publication date |
26 Jul 2015
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BAY73-4506/11728
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01289821 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Bayer HealthCare AG
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Sponsor organisation address |
Kaiser Wilhelm Allee, Leverkusen, Germany, D-51368
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Public contact |
Therapeutic Area Head, Bayer HealthCare AG, clinical-trials-contact@bayerhealthcare.com
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Scientific contact |
Therapeutic Area Head, Bayer HealthCare AG, clinical-trials-contact@bayerhealthcare.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Jun 2014
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Jun 2014
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
•Objective tumor response rate (ORR), centrally assessed
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization (ICH) guideline E6: Good Clinical Practice. Before entering the study, the ICF was read by and explained to all subjects or their legally authorized representative. Participating subjects signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
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Background therapy |
mFOLFOX6: On Day 1, subjects received 85 milligram per square meter (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, subjects 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. Thus, all mFOLFOX6 components were delivered over a total administration period of 48 hours. The next cycle of mFOLFOX6 was administered on Days 15 to 17. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Feb 2011
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
40 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 3
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Country: Number of subjects enrolled |
United States: 4
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Country: Number of subjects enrolled |
Italy: 15
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Country: Number of subjects enrolled |
United Kingdom: 11
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Country: Number of subjects enrolled |
Germany: 7
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Country: Number of subjects enrolled |
Spain: 14
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Worldwide total number of subjects |
54
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
33
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From 65 to 84 years |
21
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85 years and over |
0
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Recruitment
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Recruitment details |
Male or female subjects with histological or cytological documentation of metastatic adenocarcinoma of the colon or rectum that was unresectable or unlikely of becomining resectable, who were at least 18 years of age and were suitable to receive mFOLFOX6 regimen as first line treatment could participate in this study at 16 centers in 7 countries. | ||||||||||||||||||||||
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Pre-assignment
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Screening details |
Of 66 enrolled subjects, 54 received study medication, 4 withdrew consent during screening, and 8 were screen failures due to no measurable lesion, not suitable to receive mFOLFOX as 1st line regimen (2), uncontrolled hypertension, symptoms/signs/history of brain metastases, glomerular filtration rate too low (2), and protein in spot urine. | ||||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment Period
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
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Arms
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Arm title
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Regorafenib + Oxaliplatin/Folinic Acid/5-FU (mFOLFOX6) | ||||||||||||||||||||||
Arm description |
On Day 1, subjects received 85 milligram per square meter (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, subjects 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. Subjects received Regorafenib (Stivarga, BAY73-4506) 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Regorafenib
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Investigational medicinal product code |
BAY73-4506
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Other name |
Stivarga
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received regorafenib 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. If regorafenib was administered as a monotherapy during the study, 160 mg once daily was administered for 3 weeks on/1 week off. Doses were self-administered as four 40 mg tablets taken with 8 ounces of fluid after a low-fat breakfast.
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Investigational medicinal product name |
mFOLFOX6
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous bolus use , Intravenous use
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Dosage and administration details |
On Day 1, subjects were administered 85 mg/m^2 oxaliplatin 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 (sequential or concurrent administration was possible). Once the initial infusion was complete, subjects received a 5-FU 400 mg/m^2 IV bolus injection immediately followed by 5-FU 2400 mg/m^2 IV for 46 hours. Thus, all mFOLFOX6 components were delivered over a total administration period of 48 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17.
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Period 2
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Period 2 title |
Safety Follow-up Period
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Is this the baseline period? |
No | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
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Arms
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Arm title
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Regorafenib + Oxaliplatin/Folinic Acid/5-FU (mFOLFOX6) | ||||||||||||||||||||||
Arm description |
On Day 1, subjects received 85 mg/m^2 oxaliplatin as a 2-hour 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, subjects 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. Subjects received Regorafenib (Stivarga, BAY73-4506) 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. Subjects who had not started another anti-tumor treatment within 30 days after the last dose of study treatment, a safety follow-up visit was performed after 30 days after the last dose of study treatment. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
mFOLFOX6
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous bolus use , Intravenous use
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Dosage and administration details |
On Day 1, subjects were administered 85 mg/m^2 oxaliplatin 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 (sequential or concurrent administration was possible). Once the initial infusion was complete, subjects received a 5-FU 400 mg/m^2 IV bolus injection immediately followed by 5-FU 2400 mg/m^2 IV for 46 hours. Thus, all mFOLFOX6 components were delivered over a total administration period of 48 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17.
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Investigational medicinal product name |
Regorafenib
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Investigational medicinal product code |
BAY73-4506
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Other name |
Stivarga
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received Regorafenib 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. If Regorafenib was administered as a monotherapy during the study, 160 mg orally was administered for 3 weeks on/1 week off. Doses were self-administered as four 40 mg tablets taken with 8 ounces of fluid after a low-fat breakfast.
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Period 3
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Period 3 title |
Survival Follow-up Period
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Is this the baseline period? |
No | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
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Arms
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Arm title
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Regorafenib + Oxaliplatin/Folinic Acid/5-FU (mFOLFOX6) | ||||||||||||||||||||||
Arm description |
On Day 1, subjects received 85 mg/m^2 oxaliplatin as a 2-hour 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, subjects 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. Subjects received Regorafenib (Stivarga, BAY73-4506) 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. Subjects were evaluated bimonthly to determine their survival status up to data cut off date 30 June 2014. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Regorafenib
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Investigational medicinal product code |
BAY73-4506
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Other name |
Stivarga
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received regorafenib 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. If regorafenib was administered as a monotherapy during the study, 160 mg once daily was administered for 3 weeks on/1 week off. Doses were self-administered as four 40 mg tablets taken with 8 ounces of fluid after a low-fat breakfast.
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Investigational medicinal product name |
mFOLFOX6
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous bolus use , Intravenous use
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Dosage and administration details |
On Day 1, subjects were administered 85 mg/m^2 oxaliplatin 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 (sequential or concurrent administration was possible). Once the initial infusion was complete, subjects received a 5-FU 400 mg/m^2 IV bolus injection immediately followed by 5-FU 2400 mg/m^2 IV for 46 hours. Thus, all mFOLFOX6 components were delivered over a total administration period of 48 hours. The next cycle of mFOLFOX6 was administered on Day 15 to 17.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment Period
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Reporting group description |
On Day 1, subjects received 85 mg/m^2 oxaliplatin as a 2-hour 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, subjects 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. Subjects received Regorafenib (Stivarga, BAY73-4506) 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Regorafenib + Oxaliplatin/Folinic Acid/5-FU (mFOLFOX6)
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Reporting group description |
On Day 1, subjects received 85 milligram per square meter (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, subjects 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. Subjects received Regorafenib (Stivarga, BAY73-4506) 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. | ||
Reporting group title |
Regorafenib + Oxaliplatin/Folinic Acid/5-FU (mFOLFOX6)
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Reporting group description |
On Day 1, subjects received 85 mg/m^2 oxaliplatin as a 2-hour 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, subjects 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. Subjects received Regorafenib (Stivarga, BAY73-4506) 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. Subjects who had not started another anti-tumor treatment within 30 days after the last dose of study treatment, a safety follow-up visit was performed after 30 days after the last dose of study treatment. | ||
Reporting group title |
Regorafenib + Oxaliplatin/Folinic Acid/5-FU (mFOLFOX6)
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Reporting group description |
On Day 1, subjects received 85 mg/m^2 oxaliplatin as a 2-hour 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, subjects 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. Subjects received Regorafenib (Stivarga, BAY73-4506) 160 mg orally once daily on Days 4 to 10 and Days 18 to 24. One cycle comprised 28 days. Subjects were evaluated bimonthly to determine their survival status up to data cut off date 30 June 2014. | ||
Subject analysis set title |
Full Analysis Set (FAS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
FAS (N=54) included all subjects who received treatment.
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Subject analysis set title |
Per Protocol Set (PPS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
PPS (N=48) included all FAS subjects with no major protocol deviations affecting tumor evaluation. At least one post-baseline tumor assessment was required in order to consider the subject evaluable. Subjects who were not evaluable for tumor response and who discontinued due to a drug-related toxicity, progression by clinical judgment before disease was re-evaluated, or death were also to be considered evaluable.
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Subject analysis set title |
Primary Analysis Set (PAS)
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
PAS (N=41) was a subset of the PPS and included the first 41 subjects, who were assigned to treatment.
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End point title |
Objective Response (OR) [1] | ||||||||
End point description |
OR was defined as the best tumor response (confirmed complete response [CR] or partial response [PR]) observed by magnetic resonance imaging (MRI) or computed tomography (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 less than (<) 10 millimeter (mm). PR = At least a 30 percent (%) decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non-target lesions and no appearance of new lesions.
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End point type |
Primary
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End point timeframe |
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: EudraCT database does not allow to report only one treatment group in statistical analyses section. Due to this format constraint, charts have been uploaded with the accurate details of statistical analyses for this endpoint. Please find the statistical analyses in the attachment below. |
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Attachments |
Statistical analysis_Primary_Objective response |
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| Notes [2] - PAS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was calculated as the time from first date of receiving study treatment to date of death due to any cause. Subjects alive at the time of analysis were censored at their last date of follow-up.
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End point type |
Secondary
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End point timeframe |
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
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| Notes [3] - FAS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free Survival (PFS) | ||||||||
End point description |
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 subjects without disease progression or death at the date of database cutoff were right-censored at the last date of tumor assessment. Subjects 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.
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End point type |
Secondary
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End point timeframe |
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
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| Notes [4] - FAS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease Control (DC) | ||||||||
End point description |
DC was defined as the proportion of subjects 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.
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End point type |
Secondary
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End point timeframe |
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
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| Notes [5] - PAS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) | ||||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
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| Notes [6] - PPS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Stable Disease (DOSD) | ||||||||
End point description |
DOSD was only evaluated in subjects 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 subjects without disease progression or death before progression at the time of analysis were censored at the date of their last tumor assessment.
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End point type |
Secondary
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End point timeframe |
From start of treatment until 30 days after the last dose of study treatment, assessed by every 8 weeks
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| Notes [7] - PPS |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From start of study treatment until 4 weeks following the last dose of study treatment
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI_CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
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Reporting groups
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Reporting group title |
Regorafenib + Oxaliplatin/Folinic Acid/5-FU (mFOLFOX6)
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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25 Jul 2011 |
Amendment 1 was instituted to:
- Require additional monitoring of liver function (weekly monitoring of aspartate transaminase, alanine transaminase, and bilirubin during the first 2 cycles of regorafenib dosing was added) and to include a dose modification/interruption table specific to changes of liver function tests under treatment in accordance with the Safety Report for Health Authorities and Ethics Committees, dated 13 July 2011
- Add 2 inclusion criteria that ensured that subjects with adequate pancreatic and renal function were enrolled
- Revise the description of withdrawal of subjects from study treatment to add clinical progression to radiological progression as a condition of disease progression
- Add rules for the replacement of non-evaluable subjects for the primary endpoint
- Clarify that the administration of oxaliplatin and folinic acid could be concurrent or sequential
- Add a description of the reporting of adverse event of special interest
- Revise the definition of the FAS population to align with the intent-to-treat principle
- Rename the population analysis set to per-protocol analysis set
- Change the display of population characteristics to reflect the FAS only
- Provide miscellaneous corrections and clarifications to improved consistency throughout the document. |
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25 Feb 2014 |
Amendment 2 was instituted to specify that OS data collection would be halted as of 30 June 2014. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| ‘99999’ in the posting indicates that data were not calculated. Decimal places were automatically truncated if last decimal equals zero. | |||
