Ovarian cancer MedDRA version: 20.0 Level: PT Classification code 10033128 Term: Ovarian cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tybost
Pharmaceutical Form: Tablet
INN or Proposed INN: Cobicistat
CAS Number: 1004316-88-4
Current Sponsor code: cobicistat
Other descriptive name: COBICISTAT
Concentration unit: mg milli
Sponsors
Radboud University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A – proof of concept • Subjects who start or are on treatment with olaparib tablets 300mg BID, according to the drug label and physician’s discretion; • Subjects who are able and willing to provide written informed consent prior to screening; • Age of 18 years or older; • Able to measure the outcome of the study in this subject (e.g. patient availability; willing and being able to undergo repeated plasma sample collection); • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Part B – clinical evaluation • Subjects who start on treatment with olaparib tablets, according to the drug label and physician’s discretion; • Subjects who are able and willing to provide written informed consent prior to screening; • Age of 18 years or older; • Able to measure the outcome of the study in this subject (e.g. patient availability; willing and being able to undergo sample collection for PK and PD purposes); • Expected to be on olaparib treatment for = 3 months; • Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. 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 128 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: Part A + B • Concurrent use of other anti-cancer therapies; • Concurrent use of potent inducers or inhibitors of CYP3A4 as assessed with the KNMP “G-standaard”; • Known contra-indications for treatment with cobicistat in line with the summary of product characteristics;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A – proof-of-concept: 1.To determine the equivalence of the Area-Under-the-Curve (AUC) of the reduced, boosted dose of olaparib and the regular dose. Part B – clinical evaluation: 1.To determine if efficacy by progression-free survival (PFS) in patients with high grade ovarian cancer receiving olaparib maintenance therapy who are in response following completion of first-line platinum-based chemotherapy, treated with the lower equivalent boosted dose of olaparib is non-inferior to patients treated with the regular dose of olaparib; 2.To determine if tolerance by dose reductions due to toxicity in patients treated with the lower equivalent boosted dose of olaparib is non-inferior to patients treated with the regular dose of olaparib. ;Secondary Objective: Part A - proof-of-concept: 1.To determine whether boosting reduces the inter- and intrapatient PK variability of olaparib; 2.To describe the safety of boosted olaparib. Part B - clinical evaluation: 1.To investigate whether health status, tolerance and satisfaction of patients treated with the boosted low dose olaparib is comparable to patients treated with the regular dose of olaparib; 2.To evaluate whether treatment response of boosted versus regular olaparib can be determined with cell-free tumor nucleic acids (ctDNA) as pharmacodynamic biomarker; 3.To describe toxicity of the lower equivalent boosted dose of olaparib compared to the regular dose of olaparib; 4.To compare cost-effectiveness of the lower equivalent boosted dose of olaparib compared to the regular dose of olaparib. ;Primary end point(s): Part A – proof of concept 1.AUC0-12h for the regular and boosted olaparib will be determined using non-compartmental analysis for the primary objective. Hereto, multiple PK samples will be collected after one week of each treatment regimen at the following times: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8 hours after olaparib intake. If possible, additional PK samples will be taken after 10 and 12 ho | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A – proof of concept 1. Inter- and intrapatient variability in olaparib pharmacokinetics with and without cobicistat is calculated using non-compartmental analysis of PK data; 2. Adverse events and laboratory safety will be monitored and scored according to the CTCAEv5.0 to describe the safety of boosted olaparib treatment. Part B – clinical evaluation 1. Health status and satisfaction of patients will be monitored with the CTSQ and EQ-5D-5L questionnaires; 2. ctDNA will be determined from plasma samples; 3. Adverse events and laboratory safety will be monitored and scored according to the CTCAEv5.0 to describe the safety of boosted olaparib treatment; 4. Costs for the cost-effectiveness analysis will be assessed by the iMTA Productivity Cost Quetstionnaire (iPCQ) and iMTA Medical Consumption Questionnaires (iMCQ). Health status will be monitored with the EQ-5D-5L questionnaire. ;Timepoint(s) of evaluation of this end point: Part A - proof of concept: 1. Analysis of olaparib in plasma will be analyzed after data collection. 2. Safety assessment on every study visit Part B - clinical evaluation 1. Will be measured at baseline and after 6 and 12 weeks of therapy and every 6 months untill progression. 2. Plasma samples will be taken at baseline and after 4, 8 and 12 weeks of therapy. 3. Safety assessment on every study visit. 4. Cost questionnaires on baseline, after 6 and 12 weeks of therapy and every 6 months untill progression. | — |
Countries
Netherlands
Contacts
Public ContactNielka van Erp
Radboud University Medical Center
Outcome results
None listed