BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer
- Conditions
- Colorectal Neoplasms
- Interventions
- Registration Number
- NCT00904839
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to evaluate PFS rate at 9 months of BIBF 1120 in combination with mFolfox6 compared with mFolfox6 combined to bevacizumab in first line patients with metastatic colorectal cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 128
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BIBF 1120 + mFolfox6 BIBF 1120 BIBF1120 medium dose twice daily Bevacizumab + mFolfox6 BIBF 1120 Bevacizumab 5mg/kg once daily every other week BIBF 1120 + mFolfox6 mFolfox 6 BIBF1120 medium dose twice daily Bevacizumab + mFolfox6 mFolfox Bevacizumab 5mg/kg once daily every other week BIBF 1120 + mFolfox6 bevacizumab BIBF1120 medium dose twice daily Bevacizumab + mFolfox6 bevacizumab Bevacizumab 5mg/kg once daily every other week
- Primary Outcome Measures
Name Time Method Progression-free Survival Rate at 9 Months (PFS-9) First treatment administration to nine months PFS-9 is defined as the time from first treatment with the trial drug until either the onset of progressive disease or death. A patient is defined as progression-free for 9 months if their PFS was at least 270 days. Progression is assessed according to following mentioned RECIST criteria (version 1.0).
1. 20% increase in the sum of the longest diameter of target lesions.
2. The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
- Secondary Outcome Measures
Name Time Method Overall Survival First treatment administration until end of treatment, up to 892 days Overall survival is defined as the time from first treatment until death. Greenwood variance was used for the calculation of 95% confidence interval.
Progression-free Survival (PFS) First treatment administration until end of treatment, up to 892 days PFS is defined as the time from first treatment with the trial drug until either the onset of progressive disease or death throughout the whole study. Progression is assessed according to RECIST criteria (version 1.0). In this endpoint, the Greenwood's variance estimate was used to calculate the Kaplan-Meier progression free survival median and its corresponding 95% confidence interval
Confirmed Objective Response Rate First treatment administration until end of treatment, up to 892 days Objective response rate is defined as a best response of either complete (CR) or partial response (PR) according to RECIST version 1.0. To be assigned a status of PR or CR, changes in tumour measurements had to be confirmed by repetition of the CT or MRI scan no less than 4 weeks after the criteria for response were first met. This confirmation was necessary to avoid overestimating the response rate observed. The 95% confidence interval represent the Clopper-Pearson exact confidence interval
Unconfirmed Objective Response Rate First treatment administration until end of treatment, up to 892 days Objective response is defined as a best response of either complete (CR) or partial response (PR) according to RECIST version 1.0. To be assigned a status of PR or CR, changes in tumour measurements had to be confirmed by repetition of the CT or MRI scan no less than 4 weeks after the criteria for response were first met. This confirmation was necessary to avoid overestimating the response rate observed. The 95% Confidence interval represent the Clopper- Pearson exact confidence interval.
Resection Rate First treatment administration until end of treatment, up to 892 days Surgical excision of the lesions is allowed if the previous assessment of tumoral response occurred after at least 6 cycles of treatment. Resection Rate includes resection rates R0, R1 and R2 before progressive disease.
Peto's variance estimate was used.Tumor Shrinkage Baseline and day 85 For each patient, the minimum percentage increase from baseline measurement (≤ 28 days before the beginning of the treatment) of the sum Longest diameter (LD) of target lesions was calculated based on the measurements of tumor size. The minimum percentage increase has been divided to four groups:
1. \<= - 30%
2. \> - 30% and \< 0%
3. \>= 0% and \< 20%
4. \>=20%Incidence and Intensity of Adverse Events With Grading According CTCAE From the first dose of study medication up to 28 days after the day of the last intake of study medication, up to 920 days Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).
Percentage of Patients With Dose Limit Toxicity (DLTs) Incidence During the First Two Treatment Cycles (Phase I). First two treatment cycles, up to 28 days Percentage of patients with DLTs,AE were observed in Gastrointestinal,Hepatobiliary \& skin and subcutaneous tissue disorder.Drug related DLT was defined:1)Gastrointestinal toxicity(vomiting, nausea and diarrhoea)or hypertension of CTCAEgrade(G)3 despite optimal supportive care/intervention.2)Non-haematological toxicity of G≥3 except AE:alopecia,nail modifications,\& isolated elevation of gamma glutamyl transpeptidase.3)G4 neutropenia for\>7days(not associated with fever≥38.5°C).4)Neutropenia of G≥3 of any duration associated with fever≥38.5ºC.5)Platelets \<25,000/μLorG3 thrombocytopenia associated with bleeding requiring transfusion.6)Inability to resume nintedanib dosing within14days of stopping due to treatment related toxicity.7)ALT and/or AST elevation of G≥3orG≥2 in conjunction with bilirubin G\>1. 8)Inability to recover from increase ALT/AST in conjunction with increase of bilirubin toALT/AST toG≤1 \&bilirubin to normal or baseline within14days after nintedanib treatment interruption
Maximum Tolerable Dose (MTD) First two treatment cycles, up to 28 days Determination of Maximum Tolerable Dose based on DLT incidence.
Area Under the Plasma Concentration Time-curve Over 12 Hours for Nintedanib in the Dosing Interval at Steady State and Normalized by the Dosing Unit Administered (AUCtau,ss,Norm) (Phase I) -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h and 10h after drug administration. Area under the plasma concentration time-curve over 12 hours for Nintedanib in the dosing interval at steady state and normalized by the dosing unit administered (AUCtau,ss,norm) (Phase I)
Maximum Plasma Concentration for Nintedanib at Steady State and Normalized by the Dosing Unit Administered (Cmax,ss,Norm) (Phase I) -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h, and 10h after drug administration. Maximum plasma concentration for Nintedanib at steady state and normalized by the dosing unit administered (Cmax,ss,norm) (Phase I)
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-C30 for the Change From Baseline at 9 Months of Global Health Status Scores. Baseline and 9 months. Quality of life evaluation by a standardised questionnaires of European Organisation for Research and Treatment of Cancer (EORTC): EORTC-QLQ-C30 for the change from baseline at 9 months for Global health status scores.
Raw scores are transformed to scales of 0-100. A higher score is associated with a better quality of life for Global health status scoresQuality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months. Baseline and 9 months. Quality of life evaluation by a standardised questionnaires of European Organisation for Research and Treatment of Cancer (EORTC): EORTC-QLQ-CR38 for the change from baseline at 9 months for functional scales, Symptom scales Chemotherapy side effects .
The EORTC-QLQ-CR38 was composed of functioning scales (body image, future perspective, sexual enjoyment, sexual functioning) and symptom scales (chemotherapy side effects, defecation problems, symptoms of the gastrointestinal tract, micturition problems,female sexual problems, male sexual problems, stoma related problems, and weight loss).
Raw scores are transformed to scales of 0-100. A higher score is associated with a better quality of life for functional scales and a worse quality of life for symptom scales.Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag. from baseline until end of treatment, up to 892 days Number of participants for Quality of life evaluation by a standardised questionnaires of European Organisation for Research and Treatment of Cancer (EORTC): EORTC-QLQ-CR38 for the first use of stoma bag.
Exploratory Biomarker and Pharmacogenetic Analysis for VEGF Day 1, Day 29, Day 57, Day 85 and Day 127 Exploratory biomarker and pharmacogenetic analysis for Vascular endothelial growth factor (VEGF).
Note: This endpoint was not statistically analysed in this study.
Trial Locations
- Locations (47)
1199.51.3306C Boehringer Ingelheim Investigational Site
🇫🇷Nice Cedex 2, France
1199.51.3305A Boehringer Ingelheim Investigational Site
🇫🇷Toulouse cedex 3, France
1199.51.3308B Boehringer Ingelheim Investigational Site
🇫🇷Saint Herblain, France
1199.51.3305E Boehringer Ingelheim Investigational Site
🇫🇷Toulouse Cedex 3, France
1199.51.3308E Boehringer Ingelheim Investigational Site
🇫🇷Saint-Herblain cedex, France
1199.51.3305C Boehringer Ingelheim Investigational Site
🇫🇷Toulouse Cedex, France
1199.51.49002 Boehringer Ingelheim Investigational Site
🇩🇪Dresden, Germany
1199.51.39001 Boehringer Ingelheim Investigational Site
🇮🇹Genova, Italy
1199.51.34001 Boehringer Ingelheim Investigational Site
🇪🇸Barcelona, Spain
1199.51.39004 Boehringer Ingelheim Investigational Site
🇮🇹Macerata, Italy
1199.51.39005 Boehringer Ingelheim Investigational Site
🇮🇹Reggio Emilia, Italy
1199.51.34007 Boehringer Ingelheim Investigational Site
🇪🇸La Coruña, Spain
1199.51.32001 Boehringer Ingelheim Investigational Site
🇧🇪Leuven, Belgium
1199.51.32006 Boehringer Ingelheim Investigational Site
🇧🇪Bruxelles, Belgium
1199.51.3306A Boehringer Ingelheim Investigational Site
🇫🇷Nice Cedex 2, France
1199.51.32002 Boehringer Ingelheim Investigational Site
🇧🇪Bonheiden, Belgium
1199.51.32005 Boehringer Ingelheim Investigational Site
🇧🇪Bruxelles, Belgium
1199.51.3306D Boehringer Ingelheim Investigational Site
🇫🇷Nice Cedex 2, France
1199.51.3308D Boehringer Ingelheim Investigational Site
🇫🇷Saint-Herblain cedex, France
1199.51.3302B Boehringer Ingelheim Investigational Site
🇫🇷Villejuif Cedex, France
1199.51.49008 Boehringer Ingelheim Investigational Site
🇩🇪Schwäbisch Hall, Germany
1199.51.3301A Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1199.51.49003 Boehringer Ingelheim Investigational Site
🇩🇪Freiburg/Breisgau, Germany
1199.51.34004 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1199.51.49001 Boehringer Ingelheim Investigational Site
🇩🇪Celle, Germany
1199.51.3306B Boehringer Ingelheim Investigational Site
🇫🇷Nice Cedex 2, France
1199.51.3307A Boehringer Ingelheim Investigational Site
🇫🇷Reims Cedex, France
1199.51.3307C Boehringer Ingelheim Investigational Site
🇫🇷Reims Cedex, France
1199.51.3308C Boehringer Ingelheim Investigational Site
🇫🇷Saint Herblain, France
1199.51.3308A Boehringer Ingelheim Investigational Site
🇫🇷Saint-Herblain cedex, France
1199.51.39002 Boehringer Ingelheim Investigational Site
🇮🇹Ancona, Italy
1199.51.34006 Boehringer Ingelheim Investigational Site
🇪🇸Alicante, Spain
1199.51.3307B Boehringer Ingelheim Investigational Site
🇫🇷Reims Cedex, France
1199.51.3305B Boehringer Ingelheim Investigational Site
🇫🇷Toulouse cedex 3, France
1199.51.3302D Boehringer Ingelheim Investigational Site
🇫🇷Villejuif Cedex, France
1199.51.3302A Boehringer Ingelheim Investigational Site
🇫🇷Villejuif Cedex, France
1199.51.3302C Boehringer Ingelheim Investigational Site
🇫🇷Villejuif Cedex, France
1199.51.49006 Boehringer Ingelheim Investigational Site
🇩🇪Mainz, Germany
1199.51.49004 Boehringer Ingelheim Investigational Site
🇩🇪Halle/Saale, Germany
1199.51.39003 Boehringer Ingelheim Investigational Site
🇮🇹Udine, Italy
1199.51.34003 Boehringer Ingelheim Investigational Site
🇪🇸Madrid, Spain
1199.51.3305D Boehringer Ingelheim Investigational Site
🇫🇷Toulouse Cedex, France
1199.51.3302E Boehringer Ingelheim Investigational Site
🇫🇷Villejuif Cedex, France
1199.51.34005 Boehringer Ingelheim Investigational Site
🇪🇸Barakaldo, Spain
1199.51.3301B Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1199.51.3301D Boehringer Ingelheim Investigational Site
🇫🇷Paris, France
1199.51.3301C Boehringer Ingelheim Investigational Site
🇫🇷Paris, France