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

March 12, 2026 updated by: Centre Oscar Lambret

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
51

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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 Léonard 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
        • Hôpital Bretonneau
      • Valenciennes, France, 59300
        • Nouvelle Clinique Des Dentellières
      • Vandœuvre-lès-Nancy, France, 54 500
        • Centre Alexis Vautrin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
baseline, every 9 weeks (or 3 cycles), up to 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
response rate
Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months
according to RECIST 1.1
baseline, every 9 weeks (or 3 cycles), up to 6 months
overall survival
Time Frame: up to 2 years
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
Time Frame: baseline, every 9 weeks (or 3 cycles), up to 6 months
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
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
baseline, every 9 weeks (or 3 cycles), up to 6 months
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
baseline, every 9 weeks (or 3 cycles), up to 6 months
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
before each cycle, 3 weeks after the last dose or at the end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Centre Oscar Lambret

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Boehringer Ingelheim

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Jacques BONNETERRE, MD PhD, Oscar Lambret Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 31, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2012

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 7, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VAROCE -1206
  • 2012-002214-38 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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