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

Breast Cancer Clinical Trial

— VAROCE-1206  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01658462
• Other study ID #: VAROCE - 1206
• Secondary ID: 2012-002214-38
• Status: Completed
• Phase: Phase 2
• Start date: May 2013
• Est. completion date: October 30, 2017

Study information

• Verified date: May 2019
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: October 30, 2017
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Docetaxel
75 mg/m2 IV Day 1 / 3 weeks
• Nintedanib
200 mg x 2 per os daily from D2* *No Nintedanib on days when docetaxel is administered
• Docetaxel: increase of the dose
Dose can be increased to 100 mg/m² secondarily at cycle 2 on the initiative of the investigator

Locations

Country	Name	City	State
France	CHU Amiens- Hôpital Sud	Amiens
France	Hôpital Privé les Bonnettes	Arras
France	Centre Pierre Curie	Beuvry
France	CH Compiègne-Noyon	Compiègne
France	Centre Léonard de Vinci	Dechy
France	Centre Oscar Lambret	Lille
France	Polyclinique de Limoges - site Chénieux	Limoges
France	Institut Jean Godinot	Reims
France	CMCO de la Côte d'Opale	Saint-Martin-Boulogne
France	Hôpital Bretonneau	Tours
France	Nouvelle Clinique des Dentellières	Valenciennes
France	Centre Alexis Vautrin	Vandoeuvre Les Nancy

Sponsors (2)

Lead Sponsor	Collaborator
Centre Oscar Lambret	Boehringer Ingelheim

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	response rate	according to RECIST 1.1	baseline, every 9 weeks (or 3 cycles), up to 6 months
Secondary	overall survival	time from the date of randomization to the date of death from any cause	up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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