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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Centre Oscar Lambret
Boehringer Ingelheim
Information provided by (Responsible Party):
Centre Oscar Lambret Identifier:
First received: July 31, 2012
Last updated: November 3, 2015
Last verified: May 2015
National, randomized, unblinded, phase IIb trial with 2 strata: First-line chemotherapy / Second-line chemotherapy for locally recurrent or metastatic breast cancer.

Condition Intervention Phase
Breast Cancer
Drug: Docetaxel
Drug: Nintedanib
Drug: Docetaxel: increase of the dose
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    6-months progression free disease

Secondary Outcome Measures:
  • response rate [ Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months ] [ Designated as safety issue: Yes ]
    according to RECIST 1.1

  • overall survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    time from the date of randomization to the date of death from any cause

  • quality of life [ Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months ] [ Designated as safety issue: No ]
    EORTC QLQ C30 (Additional module BR23)

  • biological markers levels in tumors and endothelial cells [ Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months ] [ Designated as safety issue: No ]
    biological analysis of cells RT-qPCR analysis, including endothelial cells using a specific reference gene

  • biological markers in patient serum [ Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: before each cycle, 3 weeks after the last dose or at the end of study ] [ Designated as safety issue: Yes ]
    according to NCI CTCAE v3.0

Estimated Enrollment: 252
Study Start Date: May 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A
Docetaxel + Nintedanib
Drug: Docetaxel
75 mg/m2 IV Day 1 / 3 weeks
Drug: Nintedanib

200 mg x 2 per os daily from D2*

*No Nintedanib on days when docetaxel is administered

Active Comparator: Arm B
Docetaxel + increase of the dose
Drug: Docetaxel
75 mg/m2 IV Day 1 / 3 weeks
Drug: Docetaxel: increase of the dose
Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator

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


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01658462

Contact: Jacques BONNETERRE, MD PhD +33 (0)

CHU Amiens- Hôpital Sud Recruiting
Amiens, France, 80 054
Contact: Christine PIPROT, MD    +33 (0)   
Principal Investigator: Céline BIHAN, MD         
Sub-Investigator: Bruno CHAUFFERT, MD PhD         
Hôpital Privé les Bonnettes Recruiting
Arras, France, 62000
Contact: Hassan RHLIOUCH, MD    33 321210328   
Principal Investigator: Hassan RHLIOUCH, MD         
Sub-Investigator: Alexandre Mehdi HENNI, MD         
Centre Pierre Curie Not yet recruiting
Beuvry, France, 62660
Contact: Jean-Briac PREVOST, MD    +33 3 21 61 66 86   
Principal Investigator: Jean-Briac PREVOST, MD         
Sub-Investigator: Aurélie FADIN, MD         
Sub-Investigator: David DEFEVER, MD         
CH Compiègne-Noyon Recruiting
Compiègne, France, 60200
Principal Investigator: Julie VANBOCKSTAEL, MD         
Sub-Investigator: Elie Casimir NGATCHOU TAENGA, MD         
Centre Léonard de Vinci Recruiting
Dechy, France, 59 187
Contact: Claire GIRAUD, MD    +33 (0)   
Principal Investigator: Claire GIRAUD, MD         
Sub-Investigator: Virginie POTTIER, MD         
Sub-Investigator: Nicolas REZVOY, MD         
Centre Oscar Lambret Recruiting
Lille, France, 59 020
Contact: Jacques BONNETERRE, MD PhD    +33 (0)   
Principal Investigator: Jacques BONNETERRE, MD PhD         
Sub-Investigator: Audrey MAILLIEZ, MD         
Sub-Investigator: Véronique SERVENT, MD         
Sub-Investigator: Laurence VANLEMMENS, MD         
Sub-Investigator: Géraldine LAURIDANT, MD         
Sub-Investigator: Sophie COUSIN, MD         
Polyclinique de Limoges - site Chénieux Not yet recruiting
Limoges, France, 87039
Contact: Dominique GENET, MD    +33 5 55 45 48 00   
Principal Investigator: Dominique GENET, MD         
Sub-Investigator: Jean MARTIN, MD         
Sub-Investigator: Xavier ZASADNY, MD         
Sub-Investigator: Laurent ROUCHAUD, MD         
Institut Jean Godinot Recruiting
Reims, France, 51056
Contact: Hervé CURE, MD    33 3 26 50 44 87   
Principal Investigator: Hervé CURE, MD         
Sub-Investigator: Christelle JOUANNAUD, MD         
Sub-Investigator: J-Christophe EYMARD, MD         
Sub-Investigator: Aude-Marie SAVOYE, MD         
Sub-Investigator: Gabriel YAZBEK, MD         
Sub-Investigator: Brigitte COSTA, MD         
CMCO de la Côte d'Opale Recruiting
Saint Martin les Boulogne, France, 62280
Contact: Laurent GASNAULT, MD    33 321312020   
Principal Investigator: Laurent GASNAULT, MD         
Sub-Investigator: Anne-Catherine COURTECUISSE-DEGRENDEL, MD         
Hôpital Bretonneau Recruiting
Tours, France, 37044
Sub-Investigator: Philippe BOUGNOUX, MD         
Sub-Investigator: Nawale HAJJAJI, MD         
Sub-Investigator: Catherine BARBE, MD         
Sub-Investigator: M-Brigitte ORGERIE, MD         
Sub-Investigator: Dorothée CHOCTEAU-BOUJU, MD         
Sub-Investigator: Marie-Agnès BY, MD         
Nouvelle Clinique des Dentellières Recruiting
Valenciennes, France, 59300
Contact: Jessica GROSJEAN, MD    33 366227044   
Principal Investigator: Jessica GROSJEAN, MD         
Sub-Investigator: Arnaud AULIARD, MD         
Sub-Investigator: Lydie LECOMTE-DECLERCK, MD         
Centre Alexis Vautrin Recruiting
Vandoeuvre Les Nancy, France, 54 500
Contact: Maria RIOS, MD    +33 (0)   
Principal Investigator: Maria RIOS, MD         
Sub-Investigator: Mathilde DEBLOCK, MD         
Sponsors and Collaborators
Centre Oscar Lambret
Boehringer Ingelheim
Study Director: Jacques BONNETERRE, MD PhD Oscar Lambret Center
  More Information

Responsible Party: Centre Oscar Lambret Identifier: NCT01658462     History of Changes
Other Study ID Numbers: VAROCE - 1206  2012-002214-38 
Study First Received: July 31, 2012
Last Updated: November 3, 2015
Health Authority: France: Committee for the Protection of Personnes
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Centre Oscar Lambret:
locally recurrent or metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors processed this record on July 27, 2016