DOCETAXEL WITH OR WITHOUT NINTEDANIB IN PATIENT RECEIVING A SECOND-LINE OF CHEMOTHERAPY FOR HER NEGATIVE METASTATIC OR LOCALLY RECURRENT BREAST CANCER

Phase 1

• Conditions: Second-line chemotherapy for metastatic or locally recurrent breast cancer; MedDRA version: 20.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10006198Term: Breast cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-002214-38-FR
• Lead Sponsor: Centre Oscar Lambret

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-06-17
• Last Update Posted: 22 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 220

Inclusion Criteria

•Age = 18 years old
•Histologically or cytologically confirmed adenocarcinoma of the breast
•Locally recurrent or metastatic disease
•HER 2 negative status
•Relapsing after a first 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 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 < NCI CTC-AE 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 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 inheritated 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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the median PFS in patients receiving Docetaxel + Nintedanib treatment (Arm A) compared to Docetaxel alone (Arm B);Secondary Objective: To describe the safety profile of Nintedanib (NCI CTC-AE v3.0)<br>To estimate response rate and overall survival according to RECIST 1.1<br>To study the quality of life (EORTC QLQ C30 (Additional module BR23) <br>To determine VEGFR-1, -2, -3, PDGFR-a, -b and FGFR-1, -2, -3 RNA expression levels in tumors and endothelial cells<br>To determine the levels of VEGF-A, C, FGF-1, -2, PDGF-AA, -AB, -BB in patient serum<br>;Primary end point(s): Median Progression Free Survival (PFS), defined as the time from randomization to first occurrence of disease progression or death from any cause by independent review (IRF) of tumor assessments using RECIST version 1.1.;Timepoint(s) of evaluation of this end point: every 3 cycles of treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Safety according to NCI CTC-AE v3.0<br>•Response rate (RR) using RECIST version 1.1. Responses must be confirmed at least 28 days after initial documentation of response<br>•Overall survival (OS), defined as the time from the date of randomization to the date of death from any cause<br>•Quality of life: EORTC QLQ C30 (Additional module BR23)<br>•VEGFR-1, -2, -3, PDGFR-a, -b and FGFR-1, -2, -3 RNA levels determination in tumor sections by RT-qPCR analysis, including endothelial cells using a specific reference gene<br>•Dosage of VEGF-A, -C, FGF-1, -2, PDGF-AA, -AB, -BB in patient’s serum<br>;Timepoint(s) of evaluation of this end point: Efficacy, QoL and biological evaluation every 3 cycles of treament<br><br>Safety each cycle