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Phase I Comparative Bioavailability Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00777582
Recruitment Status : Active, not recruiting
First Posted : October 22, 2008
Last Update Posted : December 4, 2020
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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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

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: AZD2281 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 197 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (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
Actual Study Start Date : October 27, 2008
Actual Primary Completion Date : February 6, 2009
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Olaparib

Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. To determine the safety and tolerability of AZD2281 for both the new tablet formulation and existing capsule formulations [ Time Frame: every 28 days ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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
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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00777582


Locations
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Australia
Research Site
Randwick, Australia, 2031
Belgium
Research Site
Leuven, Belgium, 3000
Switzerland
Research Site
Bellinzona, Switzerland, CH-6500
United Kingdom
Research Site
Edinburgh, United Kingdom, EH4 2XR
Research Site
London, United Kingdom, NW1 2PG
Research Site
Manchester, United Kingdom, M20 4BX
Research Site
Newcastle upon Tyne, United Kingdom, NE7 7DN
Research Site
Northwood, United Kingdom, HA6 2RN
Research Site
Oxford, United Kingdom, OX3 7LE
Research Site
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Jane Robertson, BSc, MBCHB, MD AstraZeneca
Principal Investigator: Stan Kaye, Professor Royal Marsden NHS Foundation Trust
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00777582    
Other Study ID Numbers: D0810C00024
First Posted: October 22, 2008    Key Record Dates
Last Update Posted: December 4, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Keywords provided by AstraZeneca:
Poly (ADP ribose) polymerases
Homologous Recombination Deficiency (HRD)
Advanced solid tumours
Additional relevant MeSH terms:
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Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents