A Phase I, Open Label, 2 Part Study to Determine the Pharmacokinetics of Olaparib 300 mg bd Administered as Monotherapy and Olaparib 100 mg bd as Monotherapy and in Combination With Paclitaxel in Chinese Patients With Advanced Solid Tumours
Overview
- Phase
- Phase 1
- Intervention
- Olaparib
- Conditions
- Advanced Solid Tumours
- Sponsor
- AstraZeneca
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Steady State PK Parameter--Cmax, ss and Cmin, ss at Day 8
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a 2 parts phase I, open label trial of olaparib monotherapy and olaparib in combination with paclitaxel in patients with solid tumours. Part A will assess the single and multiple dose pharmacokinetics of olaparib monotherapy and multiple dose pharmacokinetics of olaparib in combination with paclitaxel. Part B will assess the safety of multiple doses of olaparib in Cohort 1 and of olaparib when co-administered with paclitaxel in Cohort 2
Detailed Description
Part A will access the pharmacokinetics of olaparib: Cohort 1 will investigate the single and multiple dose pharmacokinetics of olaparib following 300mg bd monotherapy dose(s); Cohort 2 will investigate the single and multiple dose pharmacokinetics of olaparib following 100mg bd monotherapy dose(s) and the multiple dose pharmacokinetics in the presence of co-administered paclitaxel (80mg/m2 weekly on days 1, 8 and 15 of a single 28-day cycle). In Part B: Safety profile of olaparib 300mg bd as monotherapy and olaparib 100mg bd in combination with weekly paclitaxel will also be investigated in Chinese patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of fully informed consent
- •Patient aged ≥ 18 years
- •Histologically or, where appropriate, cytologically confirmed malignant solid tumour refractory or resistant to standard therapy and for which no suitable effective standard therapy exists
- •life expectancy of ≥ 12 weeks
- •Patients for Cohort 2 must be eligible for paclitaxel treatment
- •Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
- •ECOG performance status ≤ 2
- •Satisfactory organ and bone marrow function measured within 28 days prior to administration of study treatment including - Haemoglobin ≥ 10.0 g/dL and no blood transfusion in the 4 weeks prior to the first dosing of study drug. - Absolute neutrophil count ≥ 1.5 × 109/L
- •Evidence of non-childbearing status for women of childbearing potential, or postmenopausal status: negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on Day
- •Patients must be on a stable concomitant medication regimen, defined as no changes in medication or in dose within 2 weeks prior to start of olaparib dosing, except for bisphosphonates, denosumab and corticosteroids, which should be stable for at least 4 weeks prior to start of olaparib dosing.
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort 1
Treat 15 patients, single dose olaparib 300mg followed by multiple dose olaparib 300mg twice a day
Intervention: Olaparib
Cohort 2
Treat 15 patients, single dose olaparib 100mg followed by multiple dose olaparib 100 mg twice a day and then in combination with paclitaxel (80mg/m2 weekly on days 1, 8 and 15 of a single 28-day cycle)
Intervention: Paclitaxel
Cohort 2
Treat 15 patients, single dose olaparib 100mg followed by multiple dose olaparib 100 mg twice a day and then in combination with paclitaxel (80mg/m2 weekly on days 1, 8 and 15 of a single 28-day cycle)
Intervention: Olaparib
Outcomes
Primary Outcomes
Steady State PK Parameter--Cmax, ss and Cmin, ss at Day 8
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 8
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - Cmax, ss and Cmin, ss (PK analysis set)
Steady State PK Parameter--AUCss at Day 9
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 9
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - AUC (PK analysis set)
Single Dose PK Parameter--AUC
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 (Day 2) and 48 h (Day 3)
Single dose PK parameter summary for olaparib in monotherapy by dose - AUC (PK analysis set)
Single Dose PK Parameter--tmax
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 (Day 2) and 48 h (Day 3)
Single dose PK parameter summary for olaparib in monotherapy by dose - tmax (PK analysis set)
Single Dose PK Parameter--t1/2, λz
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 (Day 2) and 48 h (Day 3)
Single dose PK parameter summary for olaparib in monotherapy by dose - t1/2, λz (PK analysis set)
Single Dose PK Parameter--Vz/F
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 (Day 2) and 48 h (Day 3)
Single dose PK parameter summary for olaparib in monotherapy by dose - Vz/F (PK analysis set)
Single Dose PK Parameter--CL/F
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 (Day 2) and 48 h (Day 3)
Single dose PK parameter summary for olaparib in monotherapy by dose - CL/F (PK analysis set)
Steady State PK Parameter--AUCss at Day 8
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 8
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - AUC (PK analysis set)
Steady State PK Parameter--tmax, ss at Day 8
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 8
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - tmax, ss (PK analysis set)
Single Dose PK Parameter--Cmax
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 (Day 2) and 48 h (Day 3)
Single dose PK parameter summary for olaparib in monotherapy by dose - Cmax (PK analysis set)
Steady State PK Parameter--RAC and TCP at Day 8
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 8
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - RAC and TCP (PK analysis set)
Steady State PK Parameter--Cmax, ss and Cmin, ss at Day 9
Time Frame: PK samples were collected pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 9
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - Cmax, ss and Cmin, ss (PK analysis set)
Steady State PK Parameter--tmax, ss at Day 9
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 9
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - tmax, ss (PK analysis set)
Steady State PK Parameter--CLss/F at Day 8
Time Frame: PK samples were collected pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post morning dose of Day 8
Steady state pharmacokinetic parameter summary for olaparib by dose and visit after multiple doses - CLss/F (PK analysis set)