Patients with metastatic breast cancer in 1st or 2nd line of chemotherapy MedDRA version: 16.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: AZD2014
Pharmaceutical Form: Tablet
Product Name: AZD4547
Pharmaceutical Form: Tablet
Product Name: AZD5363
Pharmaceutical Form: Capsule
Product Name: AZD8931
Pharmaceutical Form: Tab
Sponsors
UNICANCER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients who received 6 to 8 cycles of chemotherapy, or having received at least 4 cycles of chemotherapy stopped for toxicity reasons, and who are presenting a stable or a responding disease at the time of randomization 2. Patients who still meet the screening phase inclusion criteria and exclusion criteria 3. Patients whose tumor sample is presenting at least one genomic alteration from the list of predefined targetable genomic alterations and for whom the multidisciplinary tumor board has provided a personalized guidance. 4. Age = 25 years for patients planned to receive AZD4547 5. Patients will have had at least a 28-day wash-out period from last chemotherapy administration prior to randomization and should have recover (grade =1) from all residual toxicities, excluding alopecia. 6. Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, beginning 2 weeks before the first dose of investigational product and for at least 3 months after the last dose of study drug. 7. Women of childbearing potential must have a negative serum pregnancy test done within 14 days of enrollment and/or urine pregnancy test 72 hours prior to the administration of the study drug. 8. Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 3 months after the last dose. 9. Provision of signed and dated, written informed consent prior to randomization and to any study specific procedures, sampling and analysis 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 120 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 120
Exclusion criteria
Exclusion criteria: 1. No “targetable” genomic alteration identified during the screening phase (either due to the lack of alteration or due to ineligible samples for genomic analysis) or unfavorable decision from the multidisciplinary tumor board to drive the patient to the randomization. 2. More than 2 previous lines of chemotherapy for metastatic disease before randomization 3. Life expectancy 2.5x ULN in the absence of or > 5x ULN in the presence of liver metastases - bilirubin > 1.5xULN - creatinine clearance =50 mL/min (measured or calculated by Cockroft and Gault formula) - Proteinuria > 3+ on dipstick analysis or > 3.5g/24 hours or a urine protein/creatinine ratio > 3.5 (only for patients drived to receive AZD5363) - Sodium, magnesium, calcium and phosphate > ULN - Potassium 480msec (or QTcF >450 msec) obtained from 3 consecutive ECGs - LVEF <55% (MUGA scan or Echocardiogram). 13. Altered ophthalmic conditions confirmed by an ophthalmology specialist for patients likely to be treated with : - AZD4547 : current evidence or previous history of retinal pigmented epithelium detachment (RPED), previous laser treatment or intra-ocular injection for treatment of macular degeneration, current evidence or previous history of dry or wet age-related macular degeneration, current evidence or previous history of retinal vein occlusion (RVO), current evidence or previous history of retinal degenerative diseases (eg, hereditary), current evidence or previous history of any other clinically relevant chorioretinal defect - AZD8931 : any eye injury in the previous 3 months or a prior eye injury still associated with persistent or recurrent symptoms or impairment of vision, corneal surgery (laser refractive surgery performed more than 3 months prior to the start of the trial is allowed and should be recorded in surgical history), orbital irradiation, collagen vascular, chronic inflammatory or degenerative disease with eye involvement (eg, rheumatoid, Sjögren’s syndrome, systemic lupus erythematosus [SLE]), clinically significant ocula
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate whether treatment with targeted agents guided by high throughput molecular analyses (CGH array, next generation sequencing) improves overall progression-free survival as compared to standard maintenance chemotherapy in patients with metastatic breast cancer.;Secondary Objective: - To compare overall survival - To evaluate overall response rates and change in tumor size - To evaluate safety, - To explore the efficacy (response rate, change in tumor size, progression-free survival, overall survival) of the individual targeted agents, - To investigate the efficacy (response rate, change in tumor size, progression-free survival, overall survival) according to the order of preference for treatment. - To correlate molecular mechanisms in patients with the efficacy endpoints (response rate, progression-free and overall survival) ;Primary end point(s): Anti-tumor activity of all the agents, as the primary objective of the trial, will be carried out by the determination of the progression-free survival assessed in each arm of treatment. Progression-free survival (PFS) is defined as the time from randomization to the first documented progression of disease or death, whatever the cause. The tumor assessments are made by the investigators based on RECIST 1.1 criteria ([Eisenhauer 2009]). Patients still alive at the time of analysis without documented progression (including lost to follow-up) will be censored at the last known alive date. ;Timepoint(s) of evaluation of this end point: _ | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival : Overall Survival (OS) is defined as the time from randomization to death due to any cause. Patients still alive at the time of analysis (including lost to follow-up) will be censored at the last known alive date. Response and change in tumor size : Objective response (i.e. complete or partial response) will be defined using RECIST V1.1 criteria. Changes in tumor size over time will also be analysed. Safety : Evaluation of safety will be done according to NCI CTCAE v4.03 criteria. ;Timepoint(s) of evaluation of this end point: _ | — |
Countries
France
Contacts
Public ContactMarta JIMENEZ
UNICANCER
Outcome results
None listed