Tumores sólidos avanzados, cáncer de mama triple negativo Advanced Solid Tumours, Triple Negative Breast Cancer MedDRA version: 9.1 Level: LLT Classification code 10006187 Term: Breast cancer
Conditions
Interventions
Product Name: AZD2281 (KU-0059436)
Pharmaceutical Form: Capsule*
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281 (KU-0059436)
Concentration unit: mg milligram(s)
Co
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study subjects must fulfil all of the following criteria: 1. Fully-informed written consent. 2. Adequate bone marrow, hepatic and renal function including the following: - Haemoglobin =9.0 g/dL - White blood cell count >3 x 109/L - Absolute neutrophil count =1.5 x 109/L - Platelets =100 x 109/L; - Total bilirubin =1.5 x upper normal limit; - AST (SGOT), ALT (SGPT) =2.5 x upper normal limit (or =5x UNL in the presence of liver metastases); - Serum creatinine =1.5 mg/dL - Creatinine Clearance >50mL/min 3. Male or female patients, age =18 years. 4. Performance status (PS) =2 (ECOG scale). 5. The patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations. 6. Negative pregnancy test for women of childbearing potential only Phase I specific inclusion criteria: 7. Histologically confirmed metastatic cancer, not amenable to surgery or radiation therapy with curative intent. 8. Life expectancy of at least 12 weeks. 9. Patients with measurable or non measurable disease according to RECIST (see Appendix G) Phase II specific inclusion criteria: 10. All tumours must be ER-, PR- and HER-2 negative (HER-2 0,1+ by IHC; HER-2 2+ must be negative by FISH). 11. Patients with measurable disease on MRI according to appendix G 12. Breast cancer Stage Clinical T 2-3, N0 1, M0. - Patients with stage II or III breast cancer are eligible. This includes T2-3, N0 1, and M0. Cancer in the breast and/or axilla must be equal or greater than 2.0 cm. NB Patients with a HER2 negative ipsilateral breast recurrence are NOT eligible unless prior treatment consisted of excision alone for DCIS or breast conserving treatment and hormonal therapy for DCIS or invasive cancer. For inclusion in the genetic component of the study, subjects must fulfil the following criterion: · Provision of informed consent for genetic research If a subject declines to participate in the pharmacogenetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent. 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
Exclusion criteria: Any of the following is regarded as a criterion for exclusion from the study: 1. Major surgery within 4 weeks of starting the study. 2. Co-existing active infection. 3. Gastrointestinal disorders likely to interfere with absorption of the study drug (e.g. partial bowel obstruction, malabsorption) or with the patient’s ability to take regular oral medication. 4. Patients requiring treatment with inhibitors or inducers of CYP3A4. 5. Patients currently experiencing seizures or who were currently being treated with any anti-epileptic for seizures (use of anti-epileptic drugs to control pain is allowed in patients not suffering from seizures unless drug is excluded due to CYP3A4 induction – phenytoin, carbamazapine, phenobarbitone. 6. Patients who are unable to swallow oral medication. 7. A positive pregnancy test. Pregnant or breast-feeding women or women of childbearing potential unless effective methods of contraception are used (lack of childbearing potential is met by being post-menopausal, being surgical sterile, practicing contraception with an oral contraceptive or other hormonal therapy [eg, hormone implants], intra-uterine device, diaphragm with spermicide or condom with spermicide, or being sexually inactive. Patients and their partners must agree to use one of the above forms of contraception throughout the treatment period and for 3 months after discontinuation of treatment. 8. Renal dysfunction for which exposure to cisplatin would require dose modification or be completely unsafe (serum creatinine >1.5 mg/dL) 9. Immunocompromised patients e.g. Patients who are known to be serologically positive for human immunodeficiency virus (HIV). 10. Patients with active or severe cardiovascular or pulmonary disease, including recent (180 mm Hg, diastolic blood pressure >105 mm Hg), or steroid-dependent asthma, are ineligible. 11. Patients with peripheral neuropathy of any etiology that exceeds grade 1 are ineligible. 12. Patients with uncontrolled diabetes (fasting blood sugar >200 mg/dL) are ineligible. 13. Any co-existing medical condition that in the investigator’s judgement will substantially increase the risk associated with the patient’s participation in the study e.g. patients with a clinically significant hearing impairment.. 14. Simultaneous participation in any other study involving an investigational medicinal product, or having participated in a study less than 28 days prior to the start of study treatment. 15. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. 16. Known hypersensitivity to AZD2281 or any of its excipients, cisplatin or other platinum containing compounds 17. Use of live virus vaccinations within 3 months before or after treatment Phase I specific exclusion criteria: 18.Less than 28 days from active therapy (i.e. any treatment used to treat the disease) or high dose radiotherapy (patients may continue concomitant use of a stable dose of bisphosphonates if used for at least 28 days prior to commencing study treatment a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: · Part A/Phase I: The primary objective is to determine the safety and tolerability of twice daily oral doses of AZD2281 when administered in combination with cisplatin to patients with advanced solid tumours. · Part B/Phase II: The primary objective is to assess the complete pathological response rates of AZD2281+ cisplatin versus cisplatin alone in the treatment of patients with Triple Negative Breast Cancer in the neoadjuvant setting. ;Secondary Objective: The secondary objectives of the study are: 1. To compare exposure to AZD2281 when given alone and in combination with cisplatin. (Part A/Phase I). 2. To study the safety and tolerability of AZD2281 in combination with cisplatin in patients with Triple Negative Breast Cancer suitable for curative intent surgery in the neoadjuvant phase. (Part B/Phase II). 3. To make a preliminary assessment of the anti-tumour activity of AZD2281 when given in combination with cisplatin, by measuring overall response rate (Part A and B) ;Primary end point(s): Clinical endpoints (Phase II): Objective response rate: The primary objective of the Phase II part of the study is to compare complete pathological response rates between the 2 treatment groups. Surgical breast and axillary node resection specimens will be evaluated for pathologic tumour response according to NSABP guidelines (Fisher et al 2002). Patients will be considered in pCR if no invasive cancer or only in-situ cancer is observed in the breast specimen. The above system does not take into account the nodal status to define pCR. The Miller-Payne pathologic system will be use to code response. All study samples will be reviewed by two breast pathologists expert in the Miller-Payne system to provide codes for response analysis (Part B/Phase II only). | — |
Countries
Spain
Outcome results
None listed