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

• Status: Completed
• Trial end date: 2017-10-30
• Target enrollment: 0
• Participant gender: Female

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Oscar Lambret
• Collaborator: Boehringer Ingelheim
• Treatments: Docetaxel; Nintedanib

Criteria

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