This trial is active, not recruiting.

Condition breast cancer
Treatments docetaxel, nintedanib, docetaxel: increase of the dose
Phase phase 2
Sponsor Centre Oscar Lambret
Collaborator Boehringer Ingelheim
Start date May 2013
End date August 2016
Trial size 51 participants
Trial identifier NCT01658462, 2012-002214-38, VAROCE - 1206


National, randomized, unblinded, phase IIb trial with 2 strata: First-line chemotherapy / Second-line chemotherapy for locally recurrent or metastatic breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Docetaxel + Nintedanib
docetaxel Taxotere
75 mg/m2 IV Day 1 / 3 weeks
nintedanib OFEV
200 mg x 2 per os daily from D2* *No Nintedanib on days when docetaxel is administered
(Active Comparator)
Docetaxel + increase of the dose
docetaxel Taxotere
75 mg/m2 IV Day 1 / 3 weeks
docetaxel: increase of the dose Taxotere
Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator

Primary Outcomes

Progression free survival (PFS) in patients receiving Docetaxel + Nintedanib treatment (Arm A) compared to Docetaxel alone (Arm B)
time frame: baseline, every 9 weeks (or 3 cycles), up to 6 months

Secondary Outcomes

response rate
time frame: baseline, every 9 weeks (or 3 cycles), up to 6 months
overall survival
time frame: up to 2 years
quality of life
time frame: baseline, every 9 weeks (or 3 cycles), up to 6 months
biological markers levels in tumors and endothelial cells
time frame: baseline, every 9 weeks (or 3 cycles), up to 6 months
biological markers in patient serum
time frame: baseline, every 9 weeks (or 3 cycles), up to 6 months
safety profile of Nintedanib
time frame: before each cycle, 3 weeks after the last dose or at the end of study

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Age ≥ 18 years old - Histologically or cytologically confirmed adenocarcinoma of the breast - Locally recurrent or metastatic disease - HER 2 negative status - Requiring a first or a second-line chemotherapy for locally recurrent or metastatic disease. - Prior first line chemotherapy not containing Docetaxel - Measurable or evaluable disease according to RECIST 1.1 criteria - Allowed prior chemotherapy as follows : - Docetaxel in the neoadjuvant or adjuvant setting is allowed provided that relapse has been observed more than 12 months after the end of docetaxel treatment - Bevacizumab in 1st line is allowed with a wash-out of 4 weeks, with recovery to NCI-CTCAE v3.0 toxicity - ECOG performance status 0-1 - Adequate bone marrow, hepatic and renal functions as evidence by the following: - Hemoglobin ≥ 10 G/100 mL - Neutrophils count ≥ 1500 /mm3 - Platelets ≥ 100 000 /mm3 - Total bilirubin ≤ ULN (ULN:Upper Limit of Normal) - SGOT/SGPT ≤ 1.5 x ULN (≤ 2.5 x ULN in case of hepatic metastasis) - Serum alkaline phosphatase ≤ 2.5 x ULN - Creatinin clearance ≥ 45 ml/min or creatinin ≤ 1.5 x ULN - Proteinuria < CTCAE grade 2 - Coagulation parameters: International normalised ratio (INR) ≤ 2, prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 50% of deviation of institutional ULN - Effective contraception for patients (male and female) with reproductive potential during their entire participation in the study and during 3 months after the last administration of Nintedanib or Docetaxel - Negative pregnancy test (serum beta-HCG) performed within 1 week prior to start of study treatment in females with reproductive potential - Patient covered by government health insurance - Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation Exclusion Criteria: - Concomitant hormone therapy for metastatic breast cancer - Patients with dysphagia, or inability to swallow the tablets - Other serious illness or medical conditions: Cardiac disease - Unstable diabetes - Uncontrolled hypercalcemia - Pregnancy or breast feeding woman - Unable for medical follow-up (geographic, social or mental reasons) - Prior treatment with Nintedanib or any other VEGFR inhibitor - Known hypersensitivity to the trial drugs , to their excipients, to peanut, to soya or to contrast media - Contra indication to the use of the backbone treatment and to the comparator - Active brain metastases (e.g. stable for <4 weeks, no adequate previous treatment with radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone therapy will be allowed if administered as stable dose for at least one month before randomisation) - Leptomeningeal disease - Radiographic evidence of cavitary or necrotic tumors - Centrally located tumors with radiographic evidence (CT or MRI) of local invasion of major blood vessels - History of clinically significant haemorrhagic or thromboembolic event in the past 6 months - Known inherited predisposition to bleeding or thrombosis - Significant cardiovascular diseases ( i.e. uncontrolled hypertension, unstable angina, history of infarction within the past 12 months prior to start of study treatment, congestive heart failure > NYHA II, serious cardiac arrhythmia, pericardial effusion) - Other malignancies within the past 5 years other than basal cell skin cancer or carcinoma in situ of the cervix - Active serious infections in particular if requiring systemic antibiotic or antimicrobial therapy - Active or chronic hepatitis C and/or B infection - Active alcohol or drug abuse - Significant weight loss (> 10% of BW) within past 6 months prior to inclusion into the trial

Additional Information

Official title A Phase II Randomized Study of Docetaxel With or Without NINTEDANIB (BIBF-1120) in Patient Receiving a First or Second-line of Chemotherapy for HER Negative Metastatic or Locally Recurrent Breast Cancer
Description Patients will be stratified at randomization according to first-line chemotherapy / Second-line chemotherapy for metastatic or locally recurrent breast cancer Treatment until progression or unacceptable toxicity Visits are planned every 3 weeks during treatment and every 3 months after end of treatment or patient's withdrawal
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Centre Oscar Lambret.