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Phase II Study of Docetaxel +/- Nintedanib in Breast Cancer (VAROCE-1206)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01658462
Recruitment Status : Completed
First Posted : August 7, 2012
Last Update Posted : May 31, 2019
Boehringer Ingelheim
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Docetaxel Drug: Nintedanib Drug: Docetaxel: increase of the dose Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 51 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : May 2013
Actual Primary Completion Date : December 31, 2016
Actual Study Completion Date : October 30, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Arm A
Docetaxel + Nintedanib
Drug: Docetaxel
75 mg/m2 IV Day 1 / 3 weeks
Other Name: Taxotere

Drug: Nintedanib

200 mg x 2 per os daily from D2*

*No Nintedanib on days when docetaxel is administered

Other Name: OFEV

Active Comparator: Arm B
Docetaxel + increase of the dose
Drug: Docetaxel
75 mg/m2 IV Day 1 / 3 weeks
Other Name: Taxotere

Drug: Docetaxel: increase of the dose
Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator
Other Name: Taxotere

Primary Outcome Measures :
  1. 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 ]
    6-months progression free disease

Secondary Outcome Measures :
  1. response rate [ Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months ]
    according to RECIST 1.1

  2. overall survival [ Time Frame: up to 2 years ]
    time from the date of randomization to the date of death from any cause

  3. quality of life by QLQ-C30 and additionnel module BR23 [ Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months ]
    questionnaire : EORTC QLQ C30 (Additional module BR23)

  4. biological markers levels in tumors and endothelial cells [ Time Frame: 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

  5. biological markers in patient serum [ Time Frame: 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

  6. safety profile of Nintedanib [ Time Frame: before each cycle, 3 weeks after the last dose or at the end of study ]
    according to NCI CTCAE v3.0

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01658462

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CHU Amiens- Hôpital Sud
Amiens, France, 80 054
Hôpital Privé les Bonnettes
Arras, France, 62000
Centre Pierre Curie
Beuvry, France, 62660
CH Compiègne-Noyon
Compiègne, France, 60200
Centre Léonard de Vinci
Dechy, France, 59 187
Centre Oscar Lambret
Lille, France, 59 020
Polyclinique de Limoges - site Chénieux
Limoges, France, 87039
Institut Jean Godinot
Reims, France, 51056
CMCO de la Côte d'Opale
Saint-Martin-Boulogne, France, 62280
Hôpital Bretonneau
Tours, France, 37044
Nouvelle Clinique des Dentellières
Valenciennes, France, 59300
Centre Alexis Vautrin
Vandoeuvre Les Nancy, France, 54 500
Sponsors and Collaborators
Centre Oscar Lambret
Boehringer Ingelheim
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Study Director: Jacques BONNETERRE, MD PhD Oscar Lambret Center

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Responsible Party: Centre Oscar Lambret Identifier: NCT01658462    
Other Study ID Numbers: VAROCE - 1206
2012-002214-38 ( EudraCT Number )
First Posted: August 7, 2012    Key Record Dates
Last Update Posted: May 31, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Centre Oscar Lambret:
locally recurrent or metastatic breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors