Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Phase I Comparative Bioavailability Study

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00777582
First received: October 21, 2008
Last updated: November 4, 2014
Last verified: November 2014
  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:


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 ]

Enrollment: 228
Study Start Date: October 2008
Estimated Study Completion Date: December 2015
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Australia
Research Site
Randwick, Australia
Belgium
Research Site
Leuven, Belgium
Switzerland
Research Site
Bellinzona, Switzerland
United Kingdom
Research Site
Edinburgh, United Kingdom
Research Site
London, United Kingdom
Research Site
Manchester, United Kingdom
Research Site
Newcastle upon Tyne, United Kingdom
Research Site
Northwood, United Kingdom
Research Site
Oxford, United Kingdom
Research Site
Sutton, 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 by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00777582     History of Changes
Other Study ID Numbers: D0810C00024
Study First Received: October 21, 2008
Last Updated: November 4, 2014
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

ClinicalTrials.gov processed this record on November 25, 2014