Phase I Comparative Bioavailability Study

A Phase I, Randomised, 2 Period Cross Over Study to Determine the Comparative Bioavailability of Two Different Oral Formulations of AZD2281 in Cancer Patients With Advanced Solid Tumours

Sponsors

Lead Sponsor: AstraZeneca

Source AstraZeneca
Brief Summary

The purpose of this phase I randomised cross over study is to determine and compare the bioavailability of two different oral formulations of AZD2281 in advanced solid tumour cancer patients

Overall Status Active, not recruiting
Start Date October 27, 2008
Completion Date December 31, 2020
Primary Completion Date February 6, 2009
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
PK Phase Primary Outcome: To determine the comparative bioavailability of a new tablet formulation of AZD2281 compared to the existing capsule formulation Blood samples (12) will be taken at pre-defined intervals following dosing of a single capsule and a single tablet dose
Continued Supply Phase: To enable patients to continue to receive treatment with AZD2281. Safety and tolerability data will be collected to further determine the safety and tolerability of the capsule formulation of AZD2281 in these patients every 28 days
Continued Supply Expansion Phase: To compare the safety and tolerability of the tablet and capsule formulation of AZD2281 in all patients: Safety, AEs, Physical Exam, vital signs at every visit
Dose Escalation Phase of continued supply expansion: To determine safety & tolerability of higher than 200mg bid (to 400mg) of tablet & compare safety & tolerability profile of tablet with 400mg capsule at every visit
Randomised tablet formulation continued supply expansion phase (Group 8): To determine the safety and tolerability profile of selected tablet dose schedules of the melt-extrusion (tablet) formulation. at every visit
Secondary Outcome
Measure Time Frame
PK Phase Secondary Outcome: To generate single dose PK data for the new tablet formulation in man, and to generate information on dose linearity for the new tablet formulation Blood samples (12) will be taken at pre-defined intervals prior to and following dosing of a single capsule and a single tablet dose
To compare the extent of PARP inhibition achieved in peripheral blood mononuclear cells (PBMCs) following dosing of both the new tablet formulation and existing capsule formulation Blood samples (4) will be taken at pre-defined intervals prior to and following dosing of a single capsule and a single tablet dose
To determine the safety and tolerability of AZD2281 for both the new tablet formulation and existing capsule formulations every 28 days
Continued Supply Expansion Phase: To compare the steady state exposure achieved with 200mg bid tablet formulation and 400mg bid capsule formulation at visit 3 and visit 4
Continued Supply Expansion Phase: To describe the efficacy data observed in patients treated with the capsule and the tablet RECIST, Progression Free Survival, Best overall response and CA-125 response
Dose Escalation Phase of the continued supply expansion: To determine the single dose and steady state exposures achieved with higher doses of AZD2281 tablet formulation at every visit
Dose Escalation Phase of the continued supply expansion: To compare between patients the single dose and steady state exposures of AZD2281 achieved with selected tablet doses and the 400mg bid capsule dose at every visit
Dose Escalation Phase of the continued supply expansion: To describe the efficacy data observed in patients treated with the capsule formulation and the tablet formulation at every visit
Randomised tablet formulation continued supply expansion phase (Group 8): To determine the single dose and steady state exposures achieved with the selected table dose schedules of AZD2281 melt-extrusion (tablet) formulation at every visit
Randomised tablet formulation continued supply expansion phase (Group 8): To obtain a preliminary assessment of the effect of food on the exposure to AZD2281 following dosing of the melt-extrusion (tablet) formulation. at every visit
Randomised tablet formulation continued supply expansion phase (Group 8): To describe the efficacy data observed in patients treated with the melt-extrusion (tablet) formulation at every visit
Enrollment 197
Condition
Intervention

Intervention Type: Drug

Intervention Name: AZD2281

Description: Oral single dose formulation

Other Name: Olaparib

Eligibility

Criteria:

Inclusion Criteria:

- Histologically confirmed malignant advanced solid tumour, which is refractory to standard therapies (except Group 8 patients who must not be platinum refractory) or for which no suitable effective standard therapy exists

- Patients must have adequate organ and bone marrow function measured within 7 days prior to administration of study treatment

- Female patients must have evidence of non-child bearing status: negative urine or serum pregnancy test within 7 days of study treatment for women of child bearing, or postmenopausal status

Exclusion Criteria:

- Patients receiving chemotherapy, radiotherapy (except for palliative reasons) or any other anti-cancer therapy within 4 weeks of the last dose prior to study entry. Patients may continue the use of biphosphonates for bone metastases and corticosteroids

- Patients with symptomatic uncontrolled brain metastases

- Major surgery within 2 weeks of starting study and patients must have recovered from any effects of any major surgery

- Patients who are platinum refractory (Group 8 only)

- Patients with myelodysplastic syndrome/acute myeloid leukaemia (Group 8 only).

Gender: All

Minimum Age: 18 Years

Maximum Age: 130 Years

Healthy Volunteers: No

Overall Official
Location
Facility:
Research Site | Randwick, 2031, Australia
Research Site | Leuven, 3000, Belgium
Research Site | Bellinzona, CH-6500, Switzerland
Research Site | Edinburgh, EH4 2XR, United Kingdom
Research Site | London, NW1 2PG, United Kingdom
Research Site | Manchester, M20 4BX, United Kingdom
Research Site | Newcastle upon Tyne, NE7 7DN, United Kingdom
Research Site | Northwood, HA6 2RN, United Kingdom
Research Site | Oxford, OX3 7LE, United Kingdom
Research Site | Sutton, SM2 5PT, United Kingdom
Location Countries

Australia

Belgium

Switzerland

United Kingdom

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Number Of Arms 3
Arm Group

Label: Treatment A

Type: Experimental

Description: 300mg bid (twice daily) tablet dose

Label: Treatment B

Type: Experimental

Description: 400 mg twice daily (bid) capsule dose

Label: Treatment C

Type: Experimental

Description: 400mg bid (twice daily) tablet dose

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Crossover Assignment

Primary Purpose: Basic Science

Masking: None (Open Label)

Source: ClinicalTrials.gov