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

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

National, randomized, unblinded, phase IIb trial with 2 strata: First-line chemotherapy / Second-line chemotherapy for locally recurrent or metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Nintedanib; Drug: Docetaxel: increase of the dose

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

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80 054
    • CHU Amiens- Hôpital Sud
  • Arras, France, 62000
    • Hôpital Privé les Bonnettes
  • Beuvry, France, 62660
    • Centre Pierre Curie
  • Compiègne, France, 60200
    • CH Compiègne-Noyon
  • Dechy, France, 59 187
    • Centre Leonard de Vinci
  • Lille, France, 59 020
    • Centre Oscar Lambret
  • Limoges, France, 87039
    • Polyclinique de Limoges - site Chénieux
  • Reims, France, 51056
    • Institut Jean Godinot
  • Saint-Martin-Boulogne, France, 62280
    • CMCO de la Côte d'Opale
  • Tours, France, 37044
    • Hopital Bretonneau
  • Valenciennes, France, 59300
    • Nouvelle Clinique des Dentellières
  • Vandœuvre-lès-Nancy, France, 54 500
    • Centre Alexis Vautrin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Docetaxel + Nintedanib	Drug: Docetaxel; 75 mg/m2 IV Day 1 / 3 weeks; Other Names: Taxotere; Drug: Nintedanib; 200 mg x 2 per os daily from D2* *No Nintedanib on days when docetaxel is administered; Other Names: OFEV
Active Comparator: Arm B; Docetaxel + increase of the dose	Drug: Docetaxel; 75 mg/m2 IV Day 1 / 3 weeks; Other Names: 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 Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) in patients receiving Docetaxel + Nintedanib treatment (Arm A) compared to Docetaxel alone (Arm B)	6-months progression free disease	baseline, every 9 weeks (or 3 cycles), up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
response rate	according to RECIST 1.1	baseline, every 9 weeks (or 3 cycles), up to 6 months
overall survival	time from the date of randomization to the date of death from any cause	up to 2 years
quality of life by QLQ-C30 and additionnel module BR23	questionnaire : EORTC QLQ C30 (Additional module BR23)	baseline, every 9 weeks (or 3 cycles), up to 6 months
biological markers levels in tumors and endothelial cells	biological analysis of cells RT-qPCR analysis, including endothelial cells using a specific reference gene	baseline, every 9 weeks (or 3 cycles), up to 6 months
biological markers in patient serum	biological analysis in patient's serum Dosage of VEGF-A, -C, FGF-1, -2, PDGF-AA, -AB, -BB in patient's serum	baseline, every 9 weeks (or 3 cycles), up to 6 months
safety profile of Nintedanib	according to NCI CTCAE v3.0	before each cycle, 3 weeks after the last dose or at the end of study

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Collaborators: Boehringer Ingelheim
• Investigators: Study Director: Jacques BONNETERRE, MD PhD, Oscar Lambret Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2013
• Primary Completion (Actual): December 31, 2016
• Study Completion (Actual): October 30, 2017

Study Registration Dates

• First Submitted: July 31, 2012
• First Submitted That Met QC Criteria: August 6, 2012
• First Posted (Estimated): August 7, 2012

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Docetaxel; Nintedanib; locally recurrent or metastatic breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; nintedanib
• Other Study ID Numbers: VAROCE -1206; 2012-002214-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO