BRCA1 or -2 mutated breast cancer Any other cancer type expected to benefit from olaparib-carboplatin MedDRA version: 17.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 17.0
Conditions
Interventions
Product Name: Olaparib
Product Code: AZD-2281
Pharmaceutical Form: Tablet
INN or Proposed INN: Olaparib
CAS Number: 763113-22-0
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Con
Sponsors
Netherlands Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part 1: 1. Histological or cytological proof of advanced cancer pre-treated with maximally one line of systemic chemotherapy and any line of hormonal therapy and potentially benefitting from olaparib-carboplatin combination therapy; 2. Age >= 18 years; 3. Able and willing to give written informed consent; 4. WHO performance status of 0, 1 or 2; 5. Able and willing to undergo blood sampling for PK and PD analysis; 6. Life expectancy > 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity; 7. Evaluable disease according to RECIST 1.1 criteria; 8. Minimal acceptable safety laboratory values a. ANC of > 1.5 x 109 /L b. Hemoglobin of at least 5.6 mM c. Platelet count of > 100 x 10^9 /L d. Hepatic function as defined by serum bilirubin 50 mL/min (by Cockcroft-Gault formula); 9. Negative pregnancy test (urine/serum) for female patients with childbearing potential; Part 2: 1. Histological or cytological proof of advanced BRCA1 or -2 mutated HER2 negative breast cancer, without systemic chemotherapy pre-treatment for advanced disease and with any line of hormonal therapy pre-treatment; 2. Age >= 18 years; 3. Able and willing to give written informed consent; 4. WHO performance status of 0, 1 or 2; 5. Life expectancy > 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity; 6. Measureable disease according to RECIST 1.1 criteria; 7. Minimal acceptable safety laboratory values a. ANC of > 1.5 x 109 /L b. Hemoglobin of at least 5.6 mM c. Platelet count of > 100 x 109 /L d. Hepatic function as defined by serum bilirubin 50 mL/min (by Cockcroft-Gault formula); 8. Negative pregnancy test (urine/serum) for female patients with childbearing potential; 9. Pretreatment containing an anthracycline and/or taxane in the (neo-)adjuvant setting unless these treatments are not indicated. 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 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: Part 1: 1. Any treatment with investigational drugs within 28 days prior to receiving the first dose of investigational treatment; or 21 days for standard (neo-)adjuvant chemotherapy, hormonal and immunotherapy; 2. Patients who have received previous treatment with platinum compounds or high dose alkylating agents or a PARP1 inhibitor; 3. Any current treatment with drugs that induce or inhibit the CYP450 system : http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#inVivo or APPENDIX IX 4. Women who have a positive pregnancy test (urine/serum) and/or who are breast feeding; 5. Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: oral, injected or implanted hormonal methods, intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence) 6. Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1x8 Gy for pain palliation then a seven days interval should be maintained; 7. Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients; 8. Patients with known active hepatitis B or C; 9. Recent myocardial infarction (T genotype) if randomized to capecitabine 8. Women who have a positive pregnancy test (urine/serum) and/or who are breast feeding; 9. Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: oral, injected or implanted hormonal methods, intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence) 10. Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1x8 Gy for pain palliation then a seven days interval should be maintaine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To obtain the recommended phase 2 dose of the combination of carboplatin and olaparib Part 2: To compare first line treatment of BRCA-mutated HER2-negative advanced breast cancer with two cycles carboplatin-olaparib followed by olaparib monotherapy with capecitabine with progression free survival as endpoint.;Secondary Objective: Part 1: To investigate pharmacokinetics, pharmacodynamics and preliminary efficacy of the regimen Part 2: To compare first line treatment of BRCA-mutated HER2-negative advanced breast cancer with two cycles carboplatin-olaparib followed by olaparib monotherapy with capecitabine with progression free survival after second line treatment as endpoint. To determine the safety and efficacy of study treatments used in first line and second line treatment. To compare objective response rate and overall survival between the treatment arms (ie. strategy with and without carboplatin-olaparib). ;Primary end point(s): Part 1: Recommended Phase II dose Part 2: Progression Free Survival 1 Measured per RECIST version 1.1;Timepoint(s) of evaluation of this end point: Safety: continuous Tumor measurements: every 6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: List of DLTs Part 2: Progression Free Survival 2 (on second line treatment) Objective Response Rate Overall Survival ;Timepoint(s) of evaluation of this end point: Safety: continuous Tumor measurements: every 6 weeks while on study. | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Netherlands Cancer Institute
Outcome results
None listed