Breast Cancer
Conditions
Keywords
locally recurrent or metastatic breast cancer, Docetaxel, Nintedanib
Brief summary
National, randomized, unblinded, phase IIb trial with 2 strata: First-line chemotherapy / Second-line chemotherapy for locally recurrent or metastatic breast cancer.
Detailed 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
Interventions
DRUGDocetaxel
75 mg/m2 IV Day 1 / 3 weeks
DRUGNintedanib
200 mg x 2 per os daily from D2\* \*No Nintedanib on days when docetaxel is administered
DRUGDocetaxel: increase of the dose
Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator
Sponsors
Centre Oscar Lambret
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival (PFS) in patients receiving Docetaxel + Nintedanib treatment (Arm A) compared to Docetaxel alone (Arm B) | baseline, every 9 weeks (or 3 cycles), up to 6 months | 6-months progression free disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| response rate | baseline, every 9 weeks (or 3 cycles), up to 6 months | according to RECIST 1.1 |
| overall survival | up to 2 years | time from the date of randomization to the date of death from any cause |
| quality of life by QLQ-C30 and additionnel module BR23 | baseline, every 9 weeks (or 3 cycles), up to 6 months | questionnaire : EORTC QLQ C30 (Additional module BR23) |
| biological markers levels in tumors and endothelial cells | baseline, every 9 weeks (or 3 cycles), up to 6 months | biological analysis of cells RT-qPCR analysis, including endothelial cells using a specific reference gene |
| biological markers in patient serum | baseline, every 9 weeks (or 3 cycles), up to 6 months | biological analysis in patient's serum Dosage of VEGF-A, -C, FGF-1, -2, PDGF-AA, -AB, -BB in patient's serum |
| safety profile of Nintedanib | before each cycle, 3 weeks after the last dose or at the end of study | according to NCI CTCAE v3.0 |
Countries
France
Contacts
STUDY_DIRECTORJacques BONNETERRE, MD PhD
Oscar Lambret Center
Outcome results
None listed