BIBF 1120 Versus Bevacizumab in Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00904839
First received: May 18, 2009
Last updated: February 3, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms
Drug: BIBF 1120
Drug: mFolfox
Drug: Bevacizumab
Drug: mFolfox 6
Drug: bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I-II Study of BIBF 1120 and FOLFOX Compared to Bevacizumab and FOLFOX in First Line Metastatic Colorectal Cancer Patients

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Progression-free Survival Rate at 9 Months (PFS-9) [ Time Frame: First treatment administration to nine months ] [ Designated as safety issue: No ]

    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:
  • Overall Survival [ Time Frame: First treatment administration until end of treatment, up to 892 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: First treatment administration until end of treatment, up to 892 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: First treatment administration until end of treatment, up to 892 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: First treatment administration until end of treatment, up to 892 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: First treatment administration until end of treatment, up to 892 days ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and day 85 ] [ Designated as safety issue: No ]

    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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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). [ Time Frame: First two treatment cycles, up to 28 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: First two treatment cycles, up to 28 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h and 10h after drug administration. ] [ Designated as safety issue: No ]
    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) [ Time Frame: -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h, and 10h after drug administration. ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline and 9 months. ] [ Designated as safety issue: No ]

    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. [ Time Frame: Baseline and 9 months. ] [ Designated as safety issue: No ]

    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. [ Time Frame: from baseline until end of treatment, up to 892 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1, Day 29, Day 57, Day 85 and Day 127 ] [ Designated as safety issue: No ]

    Exploratory biomarker and pharmacogenetic analysis for Vascular endothelial growth factor (VEGF).

    Note: This endpoint was not statistically analysed in this study.



Enrollment: 128
Study Start Date: May 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120 + mFolfox6
BIBF1120 medium dose twice daily
Drug: BIBF 1120
BIBF 1120 100 and 150 mg capsules
Drug: mFolfox 6
IV standard chemotherapy
Drug: bevacizumab
100 mg/4 ml solution
Active Comparator: Bevacizumab + mFolfox6
Bevacizumab 5mg/kg once daily every other week
Drug: BIBF 1120
BIBF 1120 100 and 150 mg capsules
Drug: mFolfox
standard i.v chemotherapy
Drug: Bevacizumab
100 mg/Kg solution , IV infusion

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

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

Exclusion criteria:

  1. Treatment with any investigational drug within 28 days of trial onset.
  2. History of other malignancies in the last 5 years, in particular those that could affect compliance with the protocol or interpretation of results.
  3. 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,
  4. Major injuries and/or surgery or bone fracture within 4 weeks of trial inclusion, or planned surgical procedures during the trial period.
  5. Significant cardiovascular diseases
  6. History of severe haemorrhagic or thromboembolic event in the past 12 months. Known inherited predisposition to bleeding or to thrombosis.
  7. Patient with brain metastases that are symptomatic and/or require therapy.
  8. Pregnancy or breast-feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00904839

  Show 47 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00904839     History of Changes
Other Study ID Numbers: 1199.51, 2008-005364-14
Study First Received: May 18, 2009
Results First Received: November 14, 2014
Last Updated: February 3, 2015
Health Authority: Belgium: Federal Agency for Medicinal and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Spain: Spanish Agency of Medicines
United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Nintedanib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on March 25, 2015