Overview

This trial is active, not recruiting.

Condition solid tumors
Treatment azd2281
Phase phase 1
Target PARP
Sponsor AstraZeneca
Start date October 2008
End date February 2009
Trial size 228 participants
Trial identifier NCT00777582, D0810C00024

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification bio-availability study
Intervention model crossover assignment
Masking open label
Primary purpose basic science
Arm
(Experimental)
300mg bid (twice daily) tablet dose
azd2281 Olaparib
Oral single dose formulation
(Experimental)
400 mg twice daily (bid) capsule dose
azd2281 Olaparib
Oral single dose formulation
(Experimental)
400mg bid (twice daily) tablet dose
azd2281 Olaparib
Oral single dose formulation

Primary Outcomes

Measure
PK Phase Primary Outcome: To determine the comparative bioavailability of a new tablet formulation of AZD2281 compared to the existing capsule formulation
time frame: 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
time frame: 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
time frame: 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
time frame: 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.
time frame: at every visit

Secondary Outcomes

Measure
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
time frame: 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
time frame: 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
time frame: every 28 days
Continued Supply Expansion Phase: To compare the steady state exposure achieved with 200mg bid tablet formulation and 400mg bid capsule formulation
time frame: 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
time frame: 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
time frame: 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
time frame: 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
time frame: 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
time frame: 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.
time frame: 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
time frame: at every visit

Eligibility Criteria

Male or female participants from 18 years up to 130 years old.

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).

Additional Information

Official title 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
Principal investigator Stan Kaye, Professor
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by AstraZeneca.