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
概览
- 阶段
- 1 期
- 干预措施
- AZD2281
- 疾病 / 适应症
- Solid Tumors
- 发起方
- AstraZeneca
- 入组人数
- 197
- 试验地点
- 11
- 主要终点
- 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
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
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
研究者
入排标准
入选标准
- •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
排除标准
- •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).
研究组 & 干预措施
Treatment A
300mg bid (twice daily) tablet dose
干预措施: AZD2281
Treatment B
400 mg twice daily (bid) capsule dose
干预措施: AZD2281
Treatment C
400mg bid (twice daily) tablet dose
干预措施: AZD2281
结局指标
主要结局
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
时间窗: at every visit
PK Phase Primary Outcome: To determine the comparative bioavailability of a new tablet formulation of AZD2281 compared to the existing capsule formulation
时间窗: Blood samples (12) will be taken at pre-defined intervals following dosing of a single capsule and a single tablet dose
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
时间窗: 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.
时间窗: at every visit
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
时间窗: every 28 days
次要结局
- 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)
- 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(at every visit)
- 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(at every visit)
- 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 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)
- 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(at every visit)
- 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(at every visit)
- 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)
- 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.(at every visit)
- Randomised tablet formulation continued supply expansion phase (Group 8): To describe the efficacy data observed in patients treated with the melt-extrusion (tablet) formulation(at every visit)