Trial Outcomes & Findings for BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer (NCT NCT00904839)
NCT ID: NCT00904839
Last Updated: 2015-02-04
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
128 participants
Primary outcome timeframe
First treatment administration to nine months
Results posted on
2015-02-04
Participant Flow
Maximum Tolerable Dose set (MTD): The first 12-18 patients randomised to the nintedanib treatment group, treated with nintedanib according to the dose escalation part of the study. The patient randomised to MTD analysis set were in Phase-1. The final data base lock date for this study was 23 JUL 2013.
Participant milestones
| Measure |
Nintedanib 150 mg + mFolfox6
Patients receiving nintedanib 150 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Nintedanib 200 mg + mFolfox6
Patients receiving nintedanib 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Bevacizumab 5 mg + mFolfox6 (Phase II)
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
82
|
42
|
|
Overall Study
COMPLETED
|
3
|
64
|
27
|
|
Overall Study
NOT COMPLETED
|
1
|
18
|
15
|
Reasons for withdrawal
| Measure |
Nintedanib 150 mg + mFolfox6
Patients receiving nintedanib 150 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Nintedanib 200 mg + mFolfox6
Patients receiving nintedanib 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Bevacizumab 5 mg + mFolfox6 (Phase II)
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
5
|
4
|
|
Overall Study
Protocol Violation
|
0
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
2
|
0
|
|
Overall Study
Not treated
|
1
|
0
|
1
|
|
Overall Study
Other than above
|
0
|
9
|
7
|
Baseline Characteristics
BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Total
n=126 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.8 years
STANDARD_DEVIATION 9.83 • n=5 Participants
|
63.0 years
STANDARD_DEVIATION 9.36 • n=7 Participants
|
62.8 years
STANDARD_DEVIATION 9.64 • n=5 Participants
|
|
Sex: Female, Male
Female
|
39 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
46 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: First treatment administration to nine monthsPopulation: Treated Set (TS) - The treated set includes all patients who were dispensed and were documented to have taken at least one dose of the trial drug.
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.
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Progression-free Survival Rate at 9 Months (PFS-9)
|
62.1 percentage of Participants
Interval 50.2 to 73.9
|
70.2 percentage of Participants
Interval 54.5 to 85.8
|
SECONDARY outcome
Timeframe: First treatment administration until end of treatment, up to 892 daysPopulation: Treated Set (TS).
Overall survival is defined as the time from first treatment until death. Greenwood variance was used for the calculation of 95% confidence interval.
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Overall Survival
|
27.8 months
Interval 24.5 to 30.8
|
33.4 months
Interval 22.4 to
Upper confidence limit for median cannot be estimated (i.e. the confidence limits does not extend beyond the last failure time).
|
SECONDARY outcome
Timeframe: First treatment administration until end of treatment, up to 892 daysPopulation: Treated Set (TS).
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
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Progression-free Survival (PFS)
|
10.5 months
Interval 9.4 to 12.4
|
15.4 months
Interval 9.6 to 18.9
|
SECONDARY outcome
Timeframe: First treatment administration until end of treatment, up to 892 daysPopulation: Treated Set (TS).
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
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Confirmed Objective Response Rate
|
63.5 percentage of Participants
Interval 52.4 to 73.7
|
56.1 percentage of Participants
Interval 39.7 to 71.5
|
SECONDARY outcome
Timeframe: First treatment administration until end of treatment, up to 892 daysPopulation: Treated Set (TS).
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.
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Unconfirmed Objective Response Rate
|
69.4 percentage of Participants
Interval 58.5 to 79.0
|
73.2 percentage of Participants
Interval 57.1 to 85.8
|
SECONDARY outcome
Timeframe: First treatment administration until end of treatment, up to 892 daysPopulation: Treated Set (TS)
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.
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Resection Rate
|
19.5 percentage of Participants
Interval 13.0 to 26.0
|
24.5 percentage of Participants
Interval 16.6 to 32.4
|
SECONDARY outcome
Timeframe: Baseline and day 85Population: Treated Set (TS)
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%
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Tumor Shrinkage
<=-30%
|
58 participants
|
29 participants
|
|
Tumor Shrinkage
> - 30% and < 0%
|
19 participants
|
7 participants
|
|
Tumor Shrinkage
>= 0% and < 20%
|
4 participants
|
4 participants
|
|
Tumor Shrinkage
>=20%
|
2 participants
|
0 participants
|
|
Tumor Shrinkage
Non-evaluable
|
2 participants
|
1 participants
|
SECONDARY outcome
Timeframe: From the first dose of study medication up to 28 days after the day of the last intake of study medication, up to 920 daysPopulation: Treated Set (TS)
Incidence and intensity of Adverse Events with grading according to the Common Terminology Criteria for Adverse Events (CTCAE version 3.0).
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE Grade 4
|
11 participants
|
7 participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE Grade 5
|
2 participants
|
3 participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE Grade 1
|
1 participants
|
0 participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE Grade 2
|
9 participants
|
2 participants
|
|
Incidence and Intensity of Adverse Events With Grading According CTCAE
CTCAE Grade 3
|
62 participants
|
29 participants
|
SECONDARY outcome
Timeframe: First two treatment cycles, up to 28 daysPopulation: MTD set: The first 12-18 patients randomised to the nintedanib treatment group, treated with nintedanib according to the dose escalation part of the study. The outputs (updated with cleaned and more complete data) that were used to decide on the MTD of nintedanib while the study was ongoing.
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
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=3 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=9 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Percentage of Patients With Dose Limit Toxicity (DLTs) Incidence During the First Two Treatment Cycles (Phase I).
Diarrhoea
|
0.0 percentage of participants
|
11.1 percentage of participants
|
|
Percentage of Patients With Dose Limit Toxicity (DLTs) Incidence During the First Two Treatment Cycles (Phase I).
Hepatotoxicity
|
0.0 percentage of participants
|
11.1 percentage of participants
|
|
Percentage of Patients With Dose Limit Toxicity (DLTs) Incidence During the First Two Treatment Cycles (Phase I).
Rash maculo-papular
|
33.3 percentage of participants
|
0.0 percentage of participants
|
SECONDARY outcome
Timeframe: First two treatment cycles, up to 28 daysPopulation: MTD Set
Determination of Maximum Tolerable Dose based on DLT incidence.
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=3 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=9 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Maximum Tolerable Dose (MTD)
|
200 mg
|
200 mg
|
SECONDARY outcome
Timeframe: -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h and 10h after drug administration.Population: Treated Set (TS).
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)
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=3 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=4 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
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)
|
1.46 ng*h/mL/mg
Geometric Coefficient of Variation 273
|
1.53 ng*h/mL/mg
Geometric Coefficient of Variation 30.1
|
SECONDARY outcome
Timeframe: -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h, and 10h after drug administration.Population: Treated Set (TS).
Maximum plasma concentration for Nintedanib at steady state and normalized by the dosing unit administered (Cmax,ss,norm) (Phase I)
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=3 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=5 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Maximum Plasma Concentration for Nintedanib at Steady State and Normalized by the Dosing Unit Administered (Cmax,ss,Norm) (Phase I)
|
0.294 ng/mL/mg
Geometric Coefficient of Variation 319
|
0.278 ng/mL/mg
Geometric Coefficient of Variation 34.0
|
SECONDARY outcome
Timeframe: Baseline and 9 months.Population: Treated Set (TS). Number of analysed patients are the total number of patients who were analysed for the change from baseline at 9 months for Global health status scores
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 scores
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=24 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=11 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
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.
|
-1.7 units on scale
Standard Deviation 19.3
|
-9.8 units on scale
Standard Deviation 13.9
|
SECONDARY outcome
Timeframe: Baseline and 9 months.Population: Treated Set (TS)
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.
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=83 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Body image (N=24, 11)
|
-3.2 units on scale
Standard Deviation 25.3
|
-3.5 units on scale
Standard Deviation 19.0
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Future perspective (N=25, 11)
|
22.7 units on scale
Standard Deviation 35.6
|
6.1 units on scale
Standard Deviation 36.0
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Sexual enjoyment (N=2, 3)
|
-33.3 units on scale
Standard Deviation 47.1
|
-11.1 units on scale
Standard Deviation 19.2
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Sexual functioning (N=15, 7)
|
-11.1 units on scale
Standard Deviation 17.4
|
2.4 units on scale
Standard Deviation 11.5
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Chemotherapy side effects (N=25, 11)
|
20.0 units on scale
Standard Deviation 30.9
|
13.1 units on scale
Standard Deviation 13.9
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Defaecation problems (N=17, 8)
|
-5.4 units on scale
Standard Deviation 20.8
|
2.0 units on scale
Standard Deviation 7.7
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Female sexual problems (N=0, 0)
|
NA units on scale
Standard Deviation NA
There was no patient reported for this scale
|
NA units on scale
Standard Deviation NA
There was no patient reported for this scale
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Male sexual problems (N=5, 4)
|
6.7 units on scale
Standard Deviation 49.4
|
4.2 units on scale
Standard Deviation 16.0
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Micturition problems (N=25,11)
|
-5.8 units on scale
Standard Deviation 21.1
|
-7.1 units on scale
Standard Deviation 18.1
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Stoma-related problems (N=4, 2)
|
-4.8 units on scale
Standard Deviation 10.3
|
2.4 units on scale
Standard Deviation 3.4
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Symptoms area of gastro-intestinal tract (N=25,11)
|
-3.0 units on scale
Standard Deviation 13.3
|
3.4 units on scale
Standard Deviation 15.0
|
|
Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
Weight loss (N=25,11)
|
-21.3 units on scale
Standard Deviation 31.7
|
-12.1 units on scale
Standard Deviation 47.8
|
SECONDARY outcome
Timeframe: from baseline until end of treatment, up to 892 daysPopulation: Treated Set (TS).
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.
Outcome measures
| Measure |
Nintedanib + mFolfox6
n=85 Participants
Patients receiving nintedanib 150 mg or 200 mg twice daily in a form of a soft gelatine capsule plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
Bevacizumab + mFolfox6
n=41 Participants
Patients receiving bevacizumab 5 mg/kg every other week in a form of a bottles (injection concentrate solution) plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
|---|---|---|
|
Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
Baseline
|
10 participants
|
4 participants
|
|
Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
Week 6
|
3 participants
|
0 participants
|
|
Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
Week 12
|
1 participants
|
0 participants
|
|
Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
Week 24
|
1 participants
|
0 participants
|
|
Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
Week 30
|
1 participants
|
0 participants
|
|
Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
Week 54
|
1 participants
|
0 participants
|
|
Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
No use of stoma bag
|
68 participants
|
37 participants
|
SECONDARY outcome
Timeframe: Day 1, Day 29, Day 57, Day 85 and Day 127Exploratory biomarker and pharmacogenetic analysis for Vascular endothelial growth factor (VEGF). Note: This endpoint was not statistically analysed in this study.
Outcome measures
Outcome data not reported
Adverse Events
Nintedanib + mFolfox6
Serious events: 31 serious events
Other events: 84 other events
Deaths: 0 deaths
Bevacizumab + mFolfox6
Serious events: 22 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Nintedanib + mFolfox6
n=85 participants at risk
Patients receiving nintedanib 150 mg or 200 mg twice daily plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Bevacizumab + mFolfox6
n=41 participants at risk
Patients receiving bevacizumab 5 mg/kg every other week plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.2%
1/85 • 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
|
2.4%
1/41 • 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
|
|
Blood and lymphatic system disorders
Idiopathic thrombocytopenic purpura
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.4%
2/85 • 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
|
2.4%
1/41 • 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
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Cardiac disorders
Ventricular tachycardia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Gastrointestinal disorders
Abdominal pain
|
1.2%
1/85 • 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
|
4.9%
2/41 • 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
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Gastrointestinal disorders
Colonic fistula
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Gastrointestinal disorders
Diarrhoea
|
3.5%
3/85 • 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
|
7.3%
3/41 • 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
|
|
Gastrointestinal disorders
Ileus
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Gastrointestinal disorders
Inguinal hernia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Gastrointestinal disorders
Intestinal obstruction
|
3.5%
3/85 • 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
|
7.3%
3/41 • 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
|
|
Gastrointestinal disorders
Intestinal perforation
|
2.4%
2/85 • 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
|
2.4%
1/41 • 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
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Gastrointestinal disorders
Rectal perforation
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Gastrointestinal disorders
Vomiting
|
2.4%
2/85 • 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
|
4.9%
2/41 • 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
|
|
General disorders
Condition aggravated
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
General disorders
General physical health deterioration
|
1.2%
1/85 • 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
|
2.4%
1/41 • 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
|
|
General disorders
Mucosal inflammation
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
General disorders
Pyrexia
|
5.9%
5/85 • 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
|
0.00%
0/41 • 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
|
|
Hepatobiliary disorders
Cholelithiasis
|
2.4%
2/85 • 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
|
0.00%
0/41 • 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
|
|
Hepatobiliary disorders
Hepatic failure
|
2.4%
2/85 • 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
|
0.00%
0/41 • 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
|
|
Hepatobiliary disorders
Hepatotoxicity
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Abdominal abscess
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Campylobacter infection
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Infections and infestations
Device related infection
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Infections and infestations
Endocarditis staphylococcal
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Infections and infestations
Escherichia infection
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Gastroenteritis clostridial
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Liver abscess
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Infections and infestations
Perirectal abscess
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Peritonitis
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Infections and infestations
Pneumonia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Respiratory tract infection
|
2.4%
2/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Sepsis
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Infections and infestations
Viral infection
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Injury, poisoning and procedural complications
Gastrointestinal stoma complication
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Musculoskeletal and connective tissue disorders
Polyarthritis
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour associated fever
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Nervous system disorders
Dementia
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Nervous system disorders
Loss of consciousness
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Renal and urinary disorders
Renal failure
|
2.4%
2/85 • 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
|
0.00%
0/41 • 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
|
|
Renal and urinary disorders
Renal failure acute
|
2.4%
2/85 • 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
|
2.4%
1/41 • 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
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
4.7%
4/85 • 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
|
0.00%
0/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Surgical and medical procedures
Prosthesis implantation
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
|
Vascular disorders
Hypertension
|
1.2%
1/85 • 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
|
0.00%
0/41 • 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
|
|
Vascular disorders
Hypotension
|
2.4%
2/85 • 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
|
0.00%
0/41 • 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
|
|
Vascular disorders
Jugular vein thrombosis
|
0.00%
0/85 • 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
|
2.4%
1/41 • 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
|
Other adverse events
| Measure |
Nintedanib + mFolfox6
n=85 participants at risk
Patients receiving nintedanib 150 mg or 200 mg twice daily plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion).
|
Bevacizumab + mFolfox6
n=41 participants at risk
Patients receiving bevacizumab 5 mg/kg every other week plus mFolfox6: oxaliplatin 85 mg/m², l-leucovorin 200 mg/m² or d, l-leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² (bolus) and 2400 mg/m² (infusion)
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
12.9%
11/85 • 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
|
4.9%
2/41 • 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
|
|
Blood and lymphatic system disorders
Neutropenia
|
44.7%
38/85 • 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
|
34.1%
14/41 • 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
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
21.2%
18/85 • 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
|
7.3%
3/41 • 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
|
|
Ear and labyrinth disorders
Vertigo
|
5.9%
5/85 • 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
|
0.00%
0/41 • 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
|
|
Gastrointestinal disorders
Abdominal pain
|
21.2%
18/85 • 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
|
19.5%
8/41 • 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
|
|
Gastrointestinal disorders
Abdominal pain upper
|
15.3%
13/85 • 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
|
17.1%
7/41 • 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
|
|
Gastrointestinal disorders
Constipation
|
18.8%
16/85 • 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
|
46.3%
19/41 • 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
|
|
Gastrointestinal disorders
Diarrhoea
|
74.1%
63/85 • 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
|
61.0%
25/41 • 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
|
|
Gastrointestinal disorders
Dyspepsia
|
7.1%
6/85 • 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
|
7.3%
3/41 • 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
|
|
Gastrointestinal disorders
Flatulence
|
4.7%
4/85 • 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
|
7.3%
3/41 • 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
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.2%
1/85 • 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
|
7.3%
3/41 • 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
|
|
Gastrointestinal disorders
Nausea
|
70.6%
60/85 • 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
|
58.5%
24/41 • 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
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
2.4%
2/85 • 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
|
9.8%
4/41 • 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
|
|
Gastrointestinal disorders
Stomatitis
|
15.3%
13/85 • 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
|
14.6%
6/41 • 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
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/85 • 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
|
12.2%
5/41 • 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
|
|
Gastrointestinal disorders
Vomiting
|
43.5%
37/85 • 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
|
29.3%
12/41 • 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
|
|
General disorders
Asthenia
|
55.3%
47/85 • 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
|
61.0%
25/41 • 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
|
|
General disorders
Chest pain
|
5.9%
5/85 • 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
|
2.4%
1/41 • 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
|
|
General disorders
Chills
|
2.4%
2/85 • 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
|
7.3%
3/41 • 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
|
|
General disorders
Fatigue
|
30.6%
26/85 • 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
|
26.8%
11/41 • 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
|
|
General disorders
Mucosal inflammation
|
21.2%
18/85 • 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
|
39.0%
16/41 • 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
|
|
General disorders
Oedema peripheral
|
4.7%
4/85 • 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
|
9.8%
4/41 • 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
|
|
General disorders
Pain
|
7.1%
6/85 • 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
|
2.4%
1/41 • 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
|
|
General disorders
Pyrexia
|
16.5%
14/85 • 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
|
24.4%
10/41 • 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
|
|
Immune system disorders
Drug hypersensitivity
|
7.1%
6/85 • 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
|
9.8%
4/41 • 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
|
|
Infections and infestations
Nasopharyngitis
|
9.4%
8/85 • 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
|
12.2%
5/41 • 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
|
|
Infections and infestations
Urinary tract infection
|
7.1%
6/85 • 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
|
4.9%
2/41 • 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
|
|
Investigations
Alanine aminotransferase increased
|
5.9%
5/85 • 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
|
2.4%
1/41 • 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
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.9%
5/85 • 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
|
4.9%
2/41 • 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
|
|
Investigations
Weight decreased
|
9.4%
8/85 • 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
|
9.8%
4/41 • 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
|
|
Metabolism and nutrition disorders
Decreased appetite
|
30.6%
26/85 • 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
|
41.5%
17/41 • 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
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.4%
2/85 • 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
|
7.3%
3/41 • 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
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
8.2%
7/85 • 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
|
2.4%
1/41 • 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
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.4%
2/85 • 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
|
9.8%
4/41 • 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
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.9%
5/85 • 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
|
4.9%
2/41 • 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
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
3.5%
3/85 • 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
|
9.8%
4/41 • 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
|
|
Nervous system disorders
Dizziness
|
7.1%
6/85 • 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
|
14.6%
6/41 • 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
|
|
Nervous system disorders
Dysaesthesia
|
5.9%
5/85 • 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
|
7.3%
3/41 • 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
|
|
Nervous system disorders
Dysgeusia
|
18.8%
16/85 • 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
|
12.2%
5/41 • 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
|
|
Nervous system disorders
Headache
|
7.1%
6/85 • 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
|
12.2%
5/41 • 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
|
|
Nervous system disorders
Neuropathy peripheral
|
18.8%
16/85 • 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
|
17.1%
7/41 • 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
|
|
Nervous system disorders
Neurotoxicity
|
22.4%
19/85 • 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
|
31.7%
13/41 • 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
|
|
Nervous system disorders
Paraesthesia
|
36.5%
31/85 • 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
|
34.1%
14/41 • 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
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
5.9%
5/85 • 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
|
7.3%
3/41 • 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
|
|
Nervous system disorders
Polyneuropathy
|
9.4%
8/85 • 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
|
7.3%
3/41 • 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
|
|
Psychiatric disorders
Depression
|
8.2%
7/85 • 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
|
7.3%
3/41 • 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
|
|
Psychiatric disorders
Insomnia
|
5.9%
5/85 • 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
|
19.5%
8/41 • 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
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/85 • 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
|
7.3%
3/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
5/85 • 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
|
12.2%
5/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
9.4%
8/85 • 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
|
12.2%
5/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.5%
3/85 • 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
|
9.8%
4/41 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
22.4%
19/85 • 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
|
31.7%
13/41 • 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
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
9.4%
8/85 • 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
|
17.1%
7/41 • 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
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
7.1%
6/85 • 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
|
12.2%
5/41 • 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
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.5%
3/85 • 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
|
12.2%
5/41 • 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
|
|
Skin and subcutaneous tissue disorders
Nail dystrophy
|
0.00%
0/85 • 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
|
7.3%
3/41 • 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
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
10.6%
9/85 • 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
|
22.0%
9/41 • 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
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.1%
6/85 • 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
|
2.4%
1/41 • 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
|
|
Vascular disorders
Hypertension
|
17.6%
15/85 • 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
|
26.8%
11/41 • 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
|
|
Vascular disorders
Hypertensive crisis
|
1.2%
1/85 • 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
|
7.3%
3/41 • 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
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights
- Publication restrictions are in place
Restriction type: OTHER