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Phase 1

• Conditions: 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; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001652-36-FR
• Lead Sponsor: ICANCER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-01-21
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 240

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

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 < 3 months
4. Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the last chemotherapy before 4 full cycles have been delivered
5. Major surgery within 30 days (excluding placement of vascular access) or minor surgery within 14 days prior to randomisation
6. Less than 28 days from radiotherapy (wide field of radiation), less than 2 weeks from palliative radiation (limited fields). Fields should not have involved all target lesions
7. Patients treated in the last 30 days with a targeted agent in the same class as agents tested in this study
8. Participation to another clinical study with an investigational product (IP) during the last 30 days
9. History of hypersensitivity to active or inactive excipients of the study drug
10. Toxicities of grade =2 from any previous anti-cancer therapy, with the exception of alopecia
11. Altered haematopoietic or organ function, as indicated by the following criteria:
- Polynuclear neutrophils < 1.5 x 10^9/L
- Platelets < 100 x 10^9/L
- Haemoglobin < 90 g/L
- ALAT/ASAT > 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 < 4 mmol/L
- glycosylated haemoglobin (HbA1C) = 8.0% (64 mmol/mol), (only for patients supposed to receive AZD5363)
- Fasting Plasma Glucose = 7.0 mmol/L(126 mg/dL) (fasting is defined as no calorie intake for at least 8 hours)
12. Any of the following additional cardiac criteria:
- Mean resting corrected QT interval (QTc)>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

Study & Design

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