A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physician's Choice Single Agent Chemotherapy in the Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients Carrying Germline BRCA1/2 Mutations.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 266
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
Comparison of olaparib vs. physician's choice of single agent standard of care non-platinum based chemotherapy in patients with germline Breast Cancer susceptibility gene (gBRCA) mutated ovarian cancer who have progressed at least 6 months after the last platinum based chemotherapy. Patient should have received at least 2 prior lines of platinum based chemotherapy. The aim of the study is to assess the efficacy and safety of olaparib tablets.
详细描述
This open label, randomised, controlled, multi-centre study will assess the efficacy and safety of single agent olaparib vs. standard of care, based on physician's choice of single agent chemotherapy ( i.e paclitaxel, or topotecan, or pegylated liposomal doxorubicin, or gemcitabine) in platinum sensitive or partially platinum sensitive relapsed ovarian cancer patients who carry germline deleterious or suspected deleterious BRCA mutation and who have received at least 2 prior lines of platinum based chemotherapy. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients must be ≥ 18 years of age
- •Patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and/or fallopian tube cancer) or high grade endometrioid cancer. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.
- •Documented germline mutation in Breast Cancer susceptibility genes: BRCA1 and/or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
- •At least one lesion that can be accurately assessed at baseline by CT/MRI and is suitable for repeated assessment.
- •Patients must have received at least 2 prior platinum based lines of chemotherapy - Patients must be partially platinum sensitive or platinum sensitive
- •Patients must be suitable to start treatment with single agent chemotherapy based on physician's choice
- •Patients must have normal organ and bone marrow function measured within 28 days of randomisation,
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Patients must have a life expectancy ≥ 16 weeks
- •Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing.
排除标准
- •BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental
- •Exposure to any investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
- •Any previous treatment with a Polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including olaparib.
- •Patients who have platinum resistant or refractory disease
- •Patients receiving any systemic chemotherapy within 3 weeks prior to first dose of study treatment
- •Previous single agent exposure to the selected chemotherapy regimen for randomisation. - Prior malignancy in the last 5 years, unless curatively treated and recurrence free (few exceptions apply).
研究组 & 干预措施
1/OLAPARIB
olaparib 300mg oral tablets; twice daily
干预措施: OLAPARIB (Drug)
2/CHEMOTHERAPY
Physician's choice single agent chemotherapy
干预措施: Single agent chemotherapy (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
To determine the efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of Objective Response Rate (ORR) using blinded independent central review (BICR) Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment ORR is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is \< 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.
次要结局
- Time From Randomisation to Second Progression (PFS2)(Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)(RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months))
- Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population(Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Geometric Mean Plasma Concentration of Olaparib(Day 1, 1 hour post-dose and Day 29 pre-dose. DCO: 10Oct2018)
- Progression Free Survival (PFS)(RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months))
- Time From Randomization To First Subsequent Therapy Or Death (TFST)(Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Time From Randomization To Second Subsequent Therapy Or Death (TSST)(Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Overall Survival (OS)(Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death(RECIST and CA-125 follow-up assessments performed every 8 weeks (±1week), up to 48 weeks, then every 12 weeks (±1week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months))
- Duration of Response (DoR)(RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months))
- Number of Participants Who Show an Improvement in TOI Score(Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018)
- Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population(Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population(Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Number of Participants Who Experience at Least One Adverse Event (AE)(Safety Follow-up 30 days after last dose of IP, assessed from the date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Time From Randomization To Study Treatment Discontinuation Or Death (TDT)(Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Time to Response (TTR)(RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months))
- Overall Survival (OS) in BRCA Gene Population(Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))
- Mean Change From Baseline In Trial Outcome Index (TOI) Score(Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018)
- Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)(RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months))
- Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population(Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months))