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

This study is currently recruiting participants.
Verified August 2013 by Centre Oscar Lambret
Sponsor:
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01658462
First received: July 31, 2012
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

Second-line chemotherapy for metastatic or locally recurrent breast cancer


Condition Intervention Phase
Locally Recurrent or Metastatic Breast Cancer
Drug: Docetaxel
Drug: Nintedanib
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 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:
  • increase in the progression free survival (PFS) in patients receiving Docetaxel + Nintedanib treatment (Arm A) compared to Docetaxel alone (Arm B) [ Time Frame: baseline, every 3 weeks, up to 6 months ] [ Designated as safety issue: Yes ]
    6-months progression free disease


Secondary Outcome Measures:
  • response rate [ Time Frame: baseline, every 3 weeks, 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 3 weeks, 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, 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, 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


Estimated Enrollment: 220
Study Start Date: May 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: February 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 Arm B : dose can be increased to 100 mg/m2 secondarily on cycle 2
Drug: Nintedanib
200 mg x 2 per os daily 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 Arm B : dose can be increased to 100 mg/m2 secondarily on cycle 2

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years old
  • Histologically or cytologically confirmed adenocarcinoma of the breast
  • Locally recurrent or metastatic disease
  • HER 2 negative status
  • Prior first line chemotherapy not containing Docetaxel
  • Relapsing after a first line chemotherapy for locally recurrent or metastatic disease
  • Measurable or evaluable disease according to RECIST criteria
  • 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 3 months
  • 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)
    • 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) of 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) within 1 week prior to start of study treatment in females of 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:

  • Symptomatic brain metastasis
  • 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
  • Clinically significant active infections
  • Pregnancy or breast feeding woman
  • Unable for medical follow-up (geographic, social or mental reasons)
  • Prior treatment with Nintedanib or any other VEGFR inhibitor or stratify if trial aims to establish anti-angiogenic retreatment
  • Known hypersensitivity to the trial drugs , to their excipients 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01658462

Contacts
Contact: Jacques BONNETERRE, MD PhD +33 (0)3.20.29.55.50 j-bonneterre@o-lambret.fr

Locations
France
South Hospital Recruiting
Amiens, France, 80 054
Contact: Christine PIPROT, MD    +33 (0)3.22.45.56.99    pipro.christine@chu-amiens.fr   
Principal Investigator: Christine PIPROT, MD         
Sub-Investigator: Bruno CHAUFFERT, MD PhD         
Leonard de Vinci Center Recruiting
Dechy, France, 59 187
Contact: Claire GIRAULT, MD    +33 (0)3.27.08.60.63    cgiraud@clinique-psv.fr   
Principal Investigator: Claire GIRAUD, MD         
Sub-Investigator: Virginie POTTIER, MD         
Sub-Investigator: Nicolas REZVOY, MD         
Oscar Lambret Center Recruiting
Lille, France, 59 020
Contact: Jacques BONNETERRE, MD PhD    +33 (0)3.20.29.55.50    j-bonneterre@o-lambret.fr   
Principal Investigator: Jacques BONNETERRE, MD PhD         
Sub-Investigator: Audrey MAILLIEZ, MD         
Sub-Investigator: Véronique SERVENT, MD         
Sub-Investigator: Laurence VANLEMMENS, MD         
West Cancerology Institut Recruiting
St HERBLAIN, France, 44 805
Contact: Hervé CURE, MDPhD    +33 (0)3.26.50.44.87    herve.cure@reims.unicancer.fr   
Principal Investigator: Hervé CURE, MDPhD         
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         
Alexis Vautrin Center Recruiting
Vandoeuvre Les Nancy, France, 54 500
Contact: Maria RIOS, MD    +33 (0)3.83.59.85.66    m.rios@nancy.unicancer.fr   
Principal Investigator: Maria ROSS, MD         
Sub-Investigator: Mathilde DEBLOCK, MD         
Sponsors and Collaborators
Centre Oscar Lambret
Investigators
Study Director: Jacques BONNETERRE, MD PhD Oscar Lambret Center
  More Information

No publications provided

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01658462     History of Changes
Other Study ID Numbers: VAROCE - 1206
Study First Received: July 31, 2012
Last Updated: August 5, 2013
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:
Breast cancer
Docetaxel
Nintedanib

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014