phase ii study of docetaxel +/- nintedanib in breast cancer

Conditions: Breast Cancer

Summary: national, randomized, unblinded, phase iib trial with 2 strata: first-line chemotherapy / second-line chemotherapy for locally recurrent or metastatic breast cancer.

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

Eligibility criteria:
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

Keywords: locally recurrent or metastatic breast cancer docetaxel nintedanib