Clinical trial NCT00904839: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-05-20
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Progression-free Survival Rate at 9 Months (PFS-9)
timeFrame: First treatment administration to nine months
Secondary outcomes:
measure: Overall Survival
timeFrame: First treatment administration until end of treatment, up to 892 days
measure: Progression-free Survival (PFS)
timeFrame: First treatment administration until end of treatment, up to 892 days
measure: Confirmed Objective Response Rate
timeFrame: First treatment administration until end of treatment, up to 892 days
measure: Unconfirmed Objective Response Rate
timeFrame: First treatment administration until end of treatment, up to 892 days
measure: Resection Rate
timeFrame: First treatment administration until end of treatment, up to 892 days
measure: Tumor Shrinkage
timeFrame: Baseline and day 85
measure: Incidence and Intensity of Adverse Events With Grading According CTCAE
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 days
measure: Percentage of Patients With Dose Limit Toxicity (DLTs) Incidence During the First Two Treatment Cycles (Phase I).
timeFrame: First two treatment cycles, up to 28 days
measure: Maximum Tolerable Dose (MTD)
timeFrame: First two treatment cycles, up to 28 days
measure: 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)
timeFrame: -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h and 10h after drug administration.
measure: Maximum Plasma Concentration for Nintedanib at Steady State and Normalized by the Dosing Unit Administered (Cmax,ss,Norm) (Phase I)
timeFrame: -0:05h before drug administration and 1h, 2h, 2.5h, 3h, 4h, 6h, 8h, and 10h after drug administration.
measure: 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.
timeFrame: Baseline and 9 months.
measure: Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the Change From Baseline at 9 Months.
timeFrame: Baseline and 9 months.
measure: Number of Participants for Quality of Life Evaluation by a Standardised Questionnaires of EORTC: EORTC-QLQ-CR38 for the First Use of Stoma Bag.
timeFrame: from baseline until end of treatment, up to 892 days
measure: Exploratory Biomarker and Pharmacogenetic Analysis for VEGF
timeFrame: Day 1, Day 29, Day 57, Day 85 and Day 127
Other outcomes:
Locations:
city: Bonheiden
country: Belgium
facility: 1199.51.32002 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1199.51.32005 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1199.51.32006 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1199.51.32001 Boehringer Ingelheim Investigational Site
city: Nice Cedex 2
country: France
facility: 1199.51.3306A Boehringer Ingelheim Investigational Site
city: Nice Cedex 2
country: France
facility: 1199.51.3306B Boehringer Ingelheim Investigational Site
city: Nice Cedex 2
country: France
facility: 1199.51.3306C Boehringer Ingelheim Investigational Site
city: Nice Cedex 2
country: France
facility: 1199.51.3306D Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1199.51.3301A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1199.51.3301B Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1199.51.3301C Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1199.51.3301D Boehringer Ingelheim Investigational Site
city: Reims Cedex
country: France
facility: 1199.51.3307A Boehringer Ingelheim Investigational Site
city: Reims Cedex
country: France
facility: 1199.51.3307B Boehringer Ingelheim Investigational Site
city: Reims Cedex
country: France
facility: 1199.51.3307C Boehringer Ingelheim Investigational Site
city: Saint Herblain
country: France
facility: 1199.51.3308B Boehringer Ingelheim Investigational Site
city: Saint Herblain
country: France
facility: 1199.51.3308C Boehringer Ingelheim Investigational Site
city: Saint-Herblain cedex
country: France
facility: 1199.51.3308A Boehringer Ingelheim Investigational Site
city: Saint-Herblain cedex
country: France
facility: 1199.51.3308D Boehringer Ingelheim Investigational Site
city: Saint-Herblain cedex
country: France
facility: 1199.51.3308E Boehringer Ingelheim Investigational Site
city: Toulouse cedex 3
country: France
facility: 1199.51.3305A Boehringer Ingelheim Investigational Site
city: Toulouse cedex 3
country: France
facility: 1199.51.3305B Boehringer Ingelheim Investigational Site
city: Toulouse Cedex 3
country: France
facility: 1199.51.3305E Boehringer Ingelheim Investigational Site
city: Toulouse Cedex
country: France
facility: 1199.51.3305C Boehringer Ingelheim Investigational Site
city: Toulouse Cedex
country: France
facility: 1199.51.3305D Boehringer Ingelheim Investigational Site
city: Villejuif Cedex
country: France
facility: 1199.51.3302A Boehringer Ingelheim Investigational Site
city: Villejuif Cedex
country: France
facility: 1199.51.3302B Boehringer Ingelheim Investigational Site
city: Villejuif Cedex
country: France
facility: 1199.51.3302C Boehringer Ingelheim Investigational Site
city: Villejuif Cedex
country: France
facility: 1199.51.3302D Boehringer Ingelheim Investigational Site
city: Villejuif Cedex
country: France
facility: 1199.51.3302E Boehringer Ingelheim Investigational Site
city: Celle
country: Germany
facility: 1199.51.49001 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 1199.51.49002 Boehringer Ingelheim Investigational Site
city: Freiburg/Breisgau
country: Germany
facility: 1199.51.49003 Boehringer Ingelheim Investigational Site
city: Halle/Saale
country: Germany
facility: 1199.51.49004 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1199.51.49006 Boehringer Ingelheim Investigational Site
city: Schwäbisch Hall
country: Germany
facility: 1199.51.49008 Boehringer Ingelheim Investigational Site
city: Ancona
country: Italy
facility: 1199.51.39002 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1199.51.39001 Boehringer Ingelheim Investigational Site
city: Macerata
country: Italy
facility: 1199.51.39004 Boehringer Ingelheim Investigational Site
city: Reggio Emilia
country: Italy
facility: 1199.51.39005 Boehringer Ingelheim Investigational Site
city: Udine
country: Italy
facility: 1199.51.39003 Boehringer Ingelheim Investigational Site
city: Alicante
country: Spain
facility: 1199.51.34006 Boehringer Ingelheim Investigational Site
city: Barakaldo
country: Spain
facility: 1199.51.34005 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1199.51.34001 Boehringer Ingelheim Investigational Site
city: La Coruña
country: Spain
facility: 1199.51.34007 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1199.51.34003 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1199.51.34004 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: