E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
BRCA Mutated Platinum Sensitive Relapse (PSR) high grade Serous Ovarian Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014733 |
E.1.2 | Term | Endometrial cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061269 |
E.1.2 | Term | Malignant peritoneal neoplasm |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival (PFS) by investigator review of RECIST data. |
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E.5.1.1 | 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. |
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E.5.2 | 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). |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Belgium |
Brazil |
Canada |
China |
France |
Germany |
Italy |
Japan |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS (last visit last subject) undergoing the study |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |