Phase I Comparative Bioavailability Study - Full Text View

Purpose

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

Condition	Intervention	Phase
Solid Tumors	Drug: AZD2281	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Bio-availability Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
To determine the safety and tolerability of AZD2281 for both the new tablet formulation and existing capsule formulations [ Time Frame: every 28 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]

Estimated Enrollment:	185
Study Start Date:	October 2008
Estimated Study Completion Date:	March 2014
Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment A 300mg bid (twice daily) tablet dose	Drug: AZD2281 Oral single dose formulation Other Name: Olaparib
Experimental: Treatment B 400 mg twice daily (bid) capsule dose	Drug: AZD2281 Oral single dose formulation Other Name: Olaparib
Experimental: Treatment C 400mg bid (twice daily) tablet dose	Drug: AZD2281 Oral single dose formulation Other Name: Olaparib

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00777582

Locations

Australia, New South Wales
Research Site
Randwick, New South Wales, Australia
Belgium
Research Site
Leuven, Belgium
Switzerland
Research Site
Bellinzona, Switzerland
United Kingdom
Research Site
Northwood, Middlesex, United Kingdom
Research Site
Sutton, Surrey, United Kingdom
Research Site
Edinburgh, United Kingdom
Research Site
London, United Kingdom
Research Site
Manchester, United Kingdom
Research Facility
Newcastle, United Kingdom
Research Site
Oxford, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Jane Robertson, BSc, MBCHB, MD	AstraZeneca
Principal Investigator:	Stan Kaye, Professor	Royal Marsden NHS Foundation Trust

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00777582 History of Changes
Other Study ID Numbers:	D0810C00024
Study First Received:	October 21, 2008
Last Updated:	February 4, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: Research Ethics Committee

Keywords provided by AstraZeneca:

Poly (ADP ribose) polymerases
Homologous Recombination Deficiency (HRD)
Advanced solid tumours

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on May 16, 2013