Phase II Study of Docetaxel +/- Nintedanib in Breast Cancer
- Registration Number
- NCT01658462
- Lead Sponsor
- Centre Oscar Lambret
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 51
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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
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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
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ECOG performance status 0-1
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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
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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
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Negative pregnancy test (serum beta-HCG) performed within 1 week prior to start of study treatment in females with reproductive potential
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Patient covered by government health insurance
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Signed and dated written informed consent prior to admission to the study in accordance with ICH-GCP guidelines and to the local legislation
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Docetaxel Docetaxel + Nintedanib Arm B Docetaxel Docetaxel + increase of the dose Arm A Nintedanib Docetaxel + Nintedanib
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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
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)
Trial Locations
- Locations (12)
Centre Alexis Vautrin
🇫🇷Vandoeuvre Les Nancy, France
Centre Léonard de Vinci
🇫🇷Dechy, France
Institut Jean Godinot
🇫🇷Reims, France
Hôpital Privé les Bonnettes
🇫🇷Arras, France
Centre Oscar Lambret
🇫🇷Lille, France
CHU Amiens- Hôpital Sud
🇫🇷Amiens, France
Centre Pierre Curie
🇫🇷Beuvry, France
CH Compiègne-Noyon
🇫🇷Compiègne, France
Polyclinique de Limoges - site Chénieux
🇫🇷Limoges, France
CMCO de la Côte d'Opale
🇫🇷Saint-Martin-Boulogne, France
Hôpital Bretonneau
🇫🇷Tours, France
Nouvelle Clinique des Dentellières
🇫🇷Valenciennes, France