BRCA Mutated Platinum Sensitive Relapse (PSR) high grade Serous Ovarian Cancer MedDRA version: 20.0 Level: PT Classification code 10014733 Term: Endometrial cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10061269 Term: Malignant peritoneal neoplasm System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classifi
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients must be = 18 years of age. • Female patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer. • Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). • Patients who have received at least 2 previous lines of platinum containing therapy prior to randomisation For the penultimate chemotherapy course prior to enrolment on the study: • Patient defined as platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy For the last chemotherapy course immediately prior to randomisation on the study: • Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, following completion of this chemotherapy course • Patient must have received a platinum based chemotherapy regimen (eg.carboplatin or cisplatin) and have received at least 4 cycles of treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 132 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 132
Exclusion criteria
Exclusion criteria: • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). • BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., “Variants of uncertain clinical significance” or “Variant of unknown significance” or “Variant, favour polymorphism” or “benign polymorphism” etc.) • Patients who have had drainage of their ascites during the final 2 cycles of their last chemotherapy regimen prior to enrolment on the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine the efficacy by progression free survival of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.;Secondary Objective: 1. Efficacy in patients following Platinum Based Chemotherapy by assessment of overall survival 2. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen (CA-125) 3. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Efficacy in patients following Platinum Based Chemotherapy by assessment of time from randomisation to second progression 4. Health-Related Quality of Life (HRQoL) as ssessed by TOI and FACT-O 5. Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS. 6. To determine the exposure to Olaparib 7. Safety and tolerability of olaparib by assessment of the number of AEs and review of laboratory parameters ;Primary end point(s): Progression Free Survival (PFS) by investigator review of RECIST data.;Timepoint(s) of evaluation of this end point: Radiologic scans performed at base line then every ~12 weeks up to 72 weeks, then every ~ 24 weeks thereafter until objective radiological disease progression. Study data collection expected to last until 2018. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Efficacy in patients following Platinum Based Chemotherapy by assessment of overall survival 2. Efficacy in patients following Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen (CA-125) or death 3. Efficacy in patients following Platinum Based Chemotherapy by assessment of time from randomisation to second progression 4.Health-Related Quality of Life (HRQoL) as assessed by TOI and FACT-O 5. Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS. 6. To determine the exposure to Olaparib by Pharmacokinetic analysis 7. Safety and tolerability of olaparib by assessment of the number of AEs and review of laboratory parameters 8. Efficacy of olaparib by time to first subsequent therapy or death (TFST). 9. Efficacy of olaparib by time to second subsequent therapy or death (TSST). 10. Efficacy of olaparib by time from randomisation to study treatment discontinuation or death (TDT).;Timepoint(s) of evaluation of this end point: Data collection until 2018, except Pk endpt 6 1)Survival assessed 4 wkly until treatment discont, then 12 wkly 2)CA-125, baseline 4 wkly. Radiological scans, baseline, ~12 wkly until obj radiologic disease prog 3)Radiologic scans, baseline, 12 wkly for 72 wks, 24 wkly until 1st prog. As per local practice until 2nd prog 4)Paper Q's baseline, Day 29 then as per RECIST, until disease prog 5)Radiologic scans baseline, ~12 wkly for 1st 72 wks, ~24 wkly, until disease prog 6)Pk in subset of patients. Samples: Day 1+15 pre & 1 hr; Day 29 pre,0.5-1,1-3,3-6 and 6-12hrs 7.AEs from IC until post treatment 30-day follow-up. Labs until treatment discont Randomisation to:8)1st therapy or death9)2nd therapy or death10)discont or death. Assessed at 1ary PFS + final OS, data collection for ~7yrs | — |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed