A phase I/II study of carboplatin-olaparib versus capecitabine in BRCA mutated metastatic breast cancer

Phase 1

• Conditions: BRCA1 or -2 mutated breast cancerAny other cancer type expected to benefit from olaparib-carboplatin; MedDRA version: 17.0Level: PTClassification code 10057654Term: Breast cancer femaleSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.0Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 17.0Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-005590-41-NL
• Lead Sponsor: etherlands Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-10-15
• Last Update Posted: 7 June 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 130

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 < 1.5 x ULN, ASAT and ALAT <2.5 x ULN
e.Renal function as defined by serum creatinine < 1.5 x ULN or creatinine clearance > 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 < 1.5 x ULN, ASAT and ALAT < 2.5 x ULN
e.Renal function as defined by serum creatinine < 1.5 x ULN or creatinine clearance >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

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 (< six months) or unstable angina;
10.Symptomatic brain metastases. If adequately treated with resection and/or irradiation and patients are at least four weeks completely free of symptoms of these metastases and without medication related to these metastases patients could be eligible if all other in- and exclusion criteria are obeyed.
11.Known leptomeningeal metastases.
12.Any medical condition not yet specified above that is considered to possibly, probably or definitely interfere with study procedures, including adequate follow-up and compliance and/or would jeopardize safe treatment.

Part 2:
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 had previous treatment with PARP1-inhibitors, capecitabine, platinum compounds or high dose alkylating agents;
3.Treatment of advanced disease with non-hormonal therapy;
4.More than two lines of endocrine therapy for advanced disease;
5.Pretreatment not containing an anthracycline and/or taxane in the (neo-)adjuvant setting unless these treatments are not indicated
6.Any current treatment with drugs that induce or inhibit the CYP 450 system : http://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionslabeling/ucm093664.htm#inVivo or APPENDIX IX
7.DPD deficiency (determined by the DYPD*2A and 2846A>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

Study & Design

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