Phase I Comparative Bioavailability Study

Phase 1Active Not RecruitingNCT00777582

AstraZeneca197 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

197

Conditions

Solid Tumors

Interventions

AZD2281DRUG

Oral single dose formulation

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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).

Locations (10)

Research Site

Randwick, Australia

Research Site

Leuven, Belgium

Research Site

Bellinzona, Switzerland

Research Site

Edinburgh, United Kingdom

Outcomes

Primary Outcomes

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

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

Data from ClinicalTrials.gov

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