Relapsed epithelial, platinum resistant ovarian cancer with negative or unknown BRCA status MedDRA version: 14.1 Level: PT Classification code 10057529 Term: Ovarian cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Lev
Conditions
Interventions
Product Name: Veliparib
Product Code: ABT888
Pharmaceutical Form: Capsule
CAS Number: 912444-00-9
Other descriptive name: VELIPARIB
Concentration unit: mg milligram(s)
Concentration type: range
Concen
Sponsors
Vejle Hospital, Dept. of Oncology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed epithelial, primary fallopian or primary peritoneal cancer. 2. Verified progression by either RECIST criteria and/or GCIG CA125 criteria after previous first line chemotherapy or progression after later lines of cytotoxic treatment. 3. Platinum resistance or partially platinum sensitive disease - Relapsed within six months of prior first line/later lines of platinum-based therapy or - Relapsed within six-twelve months of prior first line/later lines of platinum-based therapy 4. Age = 18 years. 5. Performance status 0-2. 6. Measurable disease by RECIST 1.1 or CA125 GCIG criteria 7. Adequate bone marrow function, liver function, renal function and coagulation parameters (within 7 days prior to enrollment): WBC = 3.0 x 10^9/l or neutrophils (ANC) = 1.5 x 10^9/l Platelet count = 100 x 10^9/l Hemoglobin = 9.7 g/dl (6 mmol/L) Serum bilirubin = 1.5 x ULN Serum transaminases = 2.5 x ULN Serum creatinine = 1.5 x ULN 8. Written informed consent. 9. Tissue available for BRCAness analysis/BRCA mutation 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Prior treatment with a PARP inhibitor. 2. Patients with BRCA1/2 germline mutation. 3. Platinum-refractory disease (disease that progressed or was stable during prior platinum therapy) 4. Patients who have received (or are planning to receive) treatment with any other investigational agent, or who have participated in another clinical trial within 28 days prior to entering this trial. 5. Previous discontinuation of topotecan treatment due to toxicity, or previous dose reduction because of toxicity 6. Pregnant or breast-feeding. For fertile women a negative pregnancy test at screening is mandatory. 7. Fertile patients not willing to use acceptable and safe methods of contraception during and for 6 months after treatment 8. Other present or previous malignancy except curatively treated cervical cancer stage I, non-melanotic skin cancer or other cancer with minimal risk of relapse. Previous breast cancer is allowed, if disease free follow-up at least five years prior to enrollment. 9. CNS metastasis. 10. History of any chronic medical or psychiatric condition or laboratory abnormality, which is not medically controlled or in the opinion of the Investigator may increase the risks associated with study drug administration (e.g. diabetes, cardiac diseases, hypertension, renal or liver disease). 11. Allergy to the ingredients of the study medication.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To determine: Maximum-tolerated dose (MTD) Dose-limiting toxicities (DLT) Recommended phase II dose Phase II: To investigate response rates (based on either CA125 GCIG or RECIST criteria) of combination topotecan and veliparib (ABT888) in relapsed ovarian cancer with negative or unknown BRCA status. ;Secondary Objective: To investigate the PFS and OS in ovarian cancer patients treated with topotecan and veliparib. To investigate the clinical safety and toxicity of the treatment. ;Primary end point(s): The primary end point is 1 Maximum-tolerated dose (MTD) 2 Dose-limiting toxicities (DLT) 3 Recommended phase II dose 4 Response rates (based on RECIST version 1.1 and GCIG modified CA-125 criteria ;Timepoint(s) of evaluation of this end point: 1: Every 4 weeks 2: Every 4 weeks 4: Every 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression free survival (PFS) • Overall survival (OS) • Safety (Adverse Events (AE) and Serious Adverse Events (SAE)) • Translational research including biomarkers expressed in tumor tissue and blood and their potentially predictive or prognostic value. ;Timepoint(s) of evaluation of this end point: Every 12 weeks | — |
Countries
Denmark
Outcome results
None listed