Phase I Comparative Bioavailability Study

NCT00777582 | Active Not Recruiting Phase 1

• 2 other identifiers: D0810C000242008-003697-18
• Study Type: interventional
• Target: 197
• Locations: 4 countries
• Sites: 10

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

Conditions

Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (11)

• 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

Study Arms (3)

Treatment A

EXPERIMENTAL

300mg bid (twice daily) tablet dose

Drug: AZD2281

Treatment B

EXPERIMENTAL

400 mg twice daily (bid) capsule dose

Drug: AZD2281

Treatment C

EXPERIMENTAL

400mg bid (twice daily) tablet dose

Drug: AZD2281

Interventions

AZD2281 DRUG

Oral single dose formulation

Also known as: Olaparib

Treatment A; Treatment B; Treatment C

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (10)

Research Site

Randwick, 2031, Australia

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Bellinzona, CH-6500, Switzerland

Location

Research Site

Edinburgh, EH4 2XR, United Kingdom

Location

Research Site

London, NW1 2PG, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Research Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Research Site

Northwood, HA6 2RN, United Kingdom

Location

Research Site

Oxford, OX3 7LE, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (4)

• Mateo J, Moreno V, Gupta A, Kaye SB, Dean E, Middleton MR, Friedlander M, Gourley C, Plummer R, Rustin G, Sessa C, Leunen K, Ledermann J, Swaisland H, Fielding A, Bannister W, Nicum S, Molife LR. An Adaptive Study to Determine the Optimal Dose of the Tablet Formulation of the PARP Inhibitor Olaparib. Target Oncol. 2016 Jun;11(3):401-15. doi: 10.1007/s11523-016-0435-8.

  PMID: 27169564 DERIVED

• Matulonis UA, Penson RT, Domchek SM, Kaufman B, Shapira-Frommer R, Audeh MW, Kaye S, Molife LR, Gelmon KA, Robertson JD, Mann H, Ho TW, Coleman RL. Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety. Ann Oncol. 2016 Jun;27(6):1013-1019. doi: 10.1093/annonc/mdw133. Epub 2016 Mar 8.

  PMID: 26961146 DERIVED

• Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R, Castonguay V, De Greve J, Atkinson T, Yap TA, Sandhu S, Banerjee S, Chen LM, Friedlander ML, Kaufman B, Oza AM, Matulonis U, Barber LJ, Kozarewa I, Fenwick K, Assiotis I, Campbell J, Chen L, de Bono JS, Gore ME, Lord CJ, Ashworth A, Kaye SB. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin Cancer Res. 2013 Oct 1;19(19):5485-93. doi: 10.1158/1078-0432.CCR-13-1262. Epub 2013 Aug 6.

  PMID: 23922302 DERIVED

• Sandhu SK, Omlin A, Hylands L, Miranda S, Barber LJ, Riisnaes R, Reid AH, Attard G, Chen L, Kozarewa I, Gevensleben H, Campbell J, Fenwick K, Assiotis I, Olmos D, Yap TA, Fong P, Tunariu N, Koh D, Molife LR, Kaye S, Lord CJ, Ashworth A, de Bono J. Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol. 2013 May;24(5):1416-8. doi: 10.1093/annonc/mdt074. Epub 2013 Mar 22. No abstract available.

  PMID: 23524863 DERIVED

Related Links

• D0810C00024\_CSR\_Synopsis

MeSH Terms

Interventions

olaparib

Study Officials

• Jane Robertson, BSc, MBCHB, MD

  AstraZeneca

  STUDY DIRECTOR

• Stan Kaye, Professor

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 22, 2008
• Study Start: October 27, 2008
• Primary Completion: February 6, 2009
• Study Completion: March 31, 2026
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• 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

Locations

AU (1); GB (7); BE (1); CH (1)