Clinical trial NCT01658462: Phase II Study of Docetaxel +/- Nintedanib in Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: locally recurrent or metastatic breast cancer
Docetaxel
Nintedanib
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2012-08-07
Enrollment: 51
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Progression free survival (PFS) in patients receiving Docetaxel + Nintedanib treatment (Arm A) compared to Docetaxel alone (Arm B)
timeFrame: baseline, every 9 weeks (or 3 cycles), up to 6 months
Secondary outcomes:
measure: response rate
timeFrame: baseline, every 9 weeks (or 3 cycles), up to 6 months
measure: overall survival
timeFrame: up to 2 years
measure: quality of life by QLQ-C30 and additionnel module BR23
timeFrame: baseline, every 9 weeks (or 3 cycles), up to 6 months
measure: biological markers levels in tumors and endothelial cells
timeFrame: baseline, every 9 weeks (or 3 cycles), up to 6 months
measure: biological markers in patient serum
timeFrame: baseline, every 9 weeks (or 3 cycles), up to 6 months
measure: safety profile of Nintedanib
timeFrame: before each cycle, 3 weeks after the last dose or at the end of study
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens- Hôpital Sud
city: Arras
country: France
facility: Hôpital Privé les Bonnettes
city: Beuvry
country: France
facility: Centre Pierre Curie
city: Compiègne
country: France
facility: CH Compiègne-Noyon
city: Dechy
country: France
facility: Centre Léonard de Vinci
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: Polyclinique de Limoges - site Chénieux
city: Reims
country: France
facility: Institut Jean Godinot
city: Saint-Martin-Boulogne
country: France
facility: CMCO de la Côte d'Opale
city: Tours
country: France
facility: Hôpital Bretonneau
city: Valenciennes
country: France
facility: Nouvelle Clinique des Dentellières
city: Vandoeuvre Les Nancy
country: France
facility: Centre Alexis Vautrin
Study officials:
affiliation: Oscar Lambret Center
name: Jacques BONNETERRE, MD PhD
role: STUDY_DIRECTOR
References: