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BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer

Primary Purpose

Colorectal Neoplasms

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

BIBF 1120

mFolfox

Bevacizumab

mFolfox 6

bevacizumab

About this trial

This is an interventional treatment trial for Colorectal Neoplasms

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Age >= 18 years
Histologically proven colorectal adenocarcinoma
No previous oxaliplatin based chemotherapy is allowed unless disease free survival after the end of chemotherapy > = 12 months
No previous therapy with VEGFR or EGFR inhibitors
No prior systemic therapy for metastatic CRC
No previous adjuvant therapy with fluoropyrimidines is allowed unless disease free survival after the end of chemotherapy > 6 months
ECOG performance status < = 2
Adequate hepatic, renal and bone marrow functions:
No uncontrolled hypertension
Signed and dated written informed consent prior to admission to the study

Exclusion criteria:

Treatment with any investigational drug within 28 days of trial onset.
History of other malignancies in the last 5 years, in particular those that could affect compliance with the protocol or interpretation of results.
Serious concomitant disease, especially those affecting compliance with trial requirements or which are considered relevant for the evaluation of the efficacy or safety of the trial drug,
Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period.
Significant cardiovascular diseases
History of severe haemorrhagic or thromboembolic event in the past 12 months. Known inherited predisposition to bleeding or to thrombosis.
Patient with brain metastases that are symptomatic and/or require therapy.
Pregnancy or breast-feeding.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

BIBF 1120 + mFolfox6

Bevacizumab + mFolfox6

Arm Description

BIBF1120 medium dose twice daily

Bevacizumab 5mg/kg once daily every other week

Outcomes

Primary Outcome Measures

Progression-free Survival Rate at 9 Months (PFS-9)

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). 20% increase in the sum of the longest diameter of target lesions. The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Overall Survival

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)

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

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

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

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

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: <= - 30% > - 30% and < 0% >= 0% and < 20% >=20%

Incidence and Intensity of Adverse Events With Grading According CTCAE

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).

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)

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)

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)

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.

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

Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 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.

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

Exploratory biomarker and pharmacogenetic analysis for Vascular endothelial growth factor (VEGF). Note: This endpoint was not statistically analysed in this study.

Full Information

NCT ID

NCT00904839

First Posted

May 18, 2009

Last Updated

February 3, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00904839

Brief Title

BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer

Official Title

A Phase I-II Study of BIBF 1120 and FOLFOX Compared to Bevacizumab and FOLFOX in First Line Metastatic Colorectal Cancer Patients

Study Type

Interventional

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

May 2009 (undefined)

Primary Completion Date

January 2012 (Actual)

Study Completion Date

January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Neoplasms

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

128 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BIBF 1120 + mFolfox6

Arm Type

Experimental

Arm Description

BIBF1120 medium dose twice daily

Arm Title

Bevacizumab + mFolfox6

Arm Type

Active Comparator

Arm Description

Bevacizumab 5mg/kg once daily every other week

Intervention Type

Drug

Intervention Name(s)

BIBF 1120

Intervention Description

BIBF 1120 100 and 150 mg capsules

Intervention Type

Drug

Intervention Name(s)

BIBF 1120

Intervention Description

BIBF 1120 100 and 150 mg capsules

Intervention Type

Drug

Intervention Name(s)

mFolfox

Intervention Description

standard i.v chemotherapy

Intervention Type

Drug

Intervention Name(s)

Bevacizumab

Intervention Description

100 mg/Kg solution , IV infusion

Intervention Type

Drug

Intervention Name(s)

mFolfox 6

Intervention Description

IV standard chemotherapy

Intervention Type

Drug

Intervention Name(s)

bevacizumab

Intervention Description

100 mg/4 ml solution

Primary Outcome Measure Information:

Title

Progression-free Survival Rate at 9 Months (PFS-9)

Description

Time Frame

First treatment administration to nine months

Secondary Outcome Measure Information:

Title

Overall Survival

Description

Overall survival is defined as the time from first treatment until death. Greenwood variance was used for the calculation of 95% confidence interval.

Time Frame