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Carcinoma

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Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Olaparib/placebo tablets p.o 300mg twice daily for up to 3 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity

Olaparib/placebo tablets p.o 300mg twice daily for up to 2 years or until objective radiological disease progression as per RECIST as assessed by the Investigator. Patients with evidence of stable disease (or those who have progressed), may continue on treatment beyond 2 years, if in the patient's best interest. Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Olaparib 300mg tablets

Prof Paul DiSilvestro, MD

Prof Kathleen Moore, MD

Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients with BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer following First Line Platinum Based Chemotherapy

Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.

A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Advanced (FIGO Stage III-IV) Ovarian Cancer Following First Line Platinum Based Chemotherapy.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To determine the efficacy by progression free survival (PFS) using investigator assessment according to modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of overall survival (OS). Reports results of a pre-specified interim analysis; results for final OS analysis (235 OS events) anticipated 2029.

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen-125 (CA-125) or death

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second progression (PFS2)

To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to first subsequent therapy or death (TFST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to second subsequent therapy or death (TSST). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomisation to study treatment discontinuation or death (TDT). Reports results of a pre-specified interim analysis; final analysis results will later be added at time of final OS analysis (anticipated 2029).

To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and potential future BRCA mutation assays (gene sequencing and large rearrangement analysis)

GOG Foundation

Myriad Genetic Laboratories, Inc.

Merck Sharp & Dohme LLC

AstraZeneca

Adverse events summaries showing subjects at risk are based on those subjects who received treatment. The summary of All cause mortality showing subjects at risk are based on those subjects who are randomised (irrespective of whether received treatment or not). Note 1 subject in Global cohort placebo arm was randomised but not treated.

Olaparib 300mg Tablets (Global Cohort)

Placebo Tablets (Global Cohort)

Olaparib 300mg Tablets (China Cohort)

Placebo Tablets (China Cohort)

Olaparib 300mg Tablets (Global Cohort & China Cohort)

Placebo Tablets (Global Cohort & China Cohort)

Total

Global Cohort

China Cohort

Each study is reported in a separate row. There were 4 participants who were in both the Global and China Olaparib Arm, and 1 participant in both the Global and China Placebo Arm.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Response to previous platinum chemotherapy (as randomised)

Global Cohort (391 subjects):

260 Olaparib 131 Placebo

China Cohort (64 subjects):

44 Olaparib 20 Placebo

Included in both cohorts (5 subjects):

4 Olaparib

1 Placebo

Total (450 subjects):

300 Olaparib 150 Placebo

The data presented based on the March DCO (17 May 2018) are not the final analyses for OS, TFST, TSST, and TDT. Further analyses of these (numbered as endpoints 2, 6, 7 and 8 in Outcome Measures section) will be performed as planned in the protocol and SAP when the pre-specified number of OS events are achieved.

Elizabeth Lowe

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) \[Primary analysis\] China Full Analysis Set (FAS) consisting of all patients randomized at sites in China (including 5 patients also included in the Global Cohort).

Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) with a baseline and post baseline TOI scores available.

Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST)

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST)

Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT)

Global Full Analysis Set (FAS) consisting of all patients randomized as part of global recruitment (including 5 patients randomized in China) and confirmed as Myriad gBRCAm.

Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS

Olaparib 300mg Tablets

Placebo Tablets

Overall Study (Global Cohort)

Overall Study (China Cohort)

Immune System Diseases

Hypersensitivity

300mg Olaparib or placebo tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Placebo to match olaparib 300mg

Professor E Pujade-Lauraine, MD, PhD

A Phase III, randomised, double-blind, placebo-controlled, multi-centre study to assess the efficacy of olaparib maintenance monotherapy in relapsed high grade serous ovarian cancer (HGSOC) patients (including patients with primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer with BRCA mutations (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)) who have responded following platinum based chemotherapy.

Comparison of olaparib against a placebo in patients with ovarian cancer whose cancer has already improved by taking platinum based chemotherapy. The patients must also have a fault in their DNA which codes for the BRCA protein. The BRCA protein helps mend broken DNA in the cells of the body; if this protein doesn't work properly it can increase the chance of getting cancer. The aim of this study is to see whether patients taking olaparib tablets last longer until their cancer gets worse, compared to those taking the placebo tablet. The study is also looking to see if there is an overall improvement to how long the patients survive whilst taking olaparib tablets compared to the placebo tablets; and the quality of their life whilst living with ovarian cancer.

Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

Phase III Randomised, Double Blind, Placebo Controlled Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed BRCA Mutated Ovarian Cancer Patients With a Complete or Partial Response Following Platinum Based Chemotherapy

To determine the efficacy by progression free survival (PFS) (using investigator assessment according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)) 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.

To determine the efficacy 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 by assessment of overall survival (OS).

To determine the efficacy 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 by assessment of time to earliest progression by RECIST or CA-125 or death.

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated relapsed ovarian cancer patients who are in complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization up to second progression

To compare the effects of olaparib maintenance monotherapy compared to placebo on Health-related Quality of Life (HRQoL) as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) in BRCA mutated relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy. The TOI ranges from 0-100 and a higher score indicates a higher HRQoL.

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to first subsequent therapy or death (TFST).

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to second subsequent therapy or death (TSST).

To determine the efficacy of olaparib maintenance monotherapy compared to placebo in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy by assessment of time from randomization to study treatment discontinuation or death (TDT).

To assess efficacy of olaparib in patients identified as having a deleterious or suspected deleterious variant in either of the BRCA genes using variants identified with current and future BRCA mutation assays (gene sequencing and large rearrangement analysis).

To determine the exposure to olaparib in patients receiving olaparib maintenance monotherapy

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Olaparib 300 Tablets (Global Cohort)

Olaparib 300 Tablets (China Cohort)

There are 196 Olaparib patients in the Global Cohort and 22 in the China Cohort (Total = 218).

There are 99 Placebo patients in the Global Cohort and 10 in the China Cohort (Total = 109)

There are 196 Olaparib patients in the Global Cohort and 22 in the China Cohort (Total = 218). There are 99 Placebo patients in the Global Cohort and 10 in the China Cohort (Total = 109)

Age, Customized

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Global Cohort: 196 Olaparib, 99 Placebo China Cohort: 22 Olaparib, 10 Placebo

The outbreak of the COVID-19 pandemic shortly before the final OS DCO (03 February 2020) was not judged to meaningfully impact the overall quality of the study, including the conduct, data, and interpretation of results.

Global Clinical Program Lead

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment, excluding China \[Primary analysis\] China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1)

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China) China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Overall Survival

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China).

China Full Analysis Set (FAS) includes all patients who were randomised at sites in China.

Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time to Earliest Progression by RECIST or Cancer Antigen (CA-125) or Death

Efficacy in Patients Following Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China) with a baseline and post baseline TOI score available \[This endpoint was not assessed in the China Cohort\]

Efficacy of Olaparib by Time to First Subsequent Therapy or Death (TFST)

Olaparib 300mg Tablets (ChinaCohort)

Efficacy of Olaparib by Time to Second Subsequent Therapy or Death (TSST)

Efficacy of Olaparib by Time From Randomization to Study Treatment Discontinuation or Death (TDT)

Full Analysis Set (FAS) consisting of all patients randomized as part of global enrolment (excluding China) and confirmed as Myriad gBRCAm \[This endpoint was not assessed in the China Cohort\]

Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS.

Day 1 - Pre-dose

Day 1 - 1 hour

Day 15 - Pre-dose

Day 15 - 1 hour

Day 29 - Pre-dose

Pharmacokinetic (PK) Analysis Set - all patients who receive study treatment as per protocol, do not violate or deviate from the protocol in ways that would significantly affect the PK analyses and have valid PK data.

The PK Analysis Set is a subset of the Global FAS; PK analysis was not performed in the China Cohort.

To Determine the Exposure to Olaparib by Pharmacokinetic Analysis

Overall Study

300mg Olaparib tablets taken orally twice daily until objective radiological disease progression as per RECIST as assessed by the investigator (or as long as in the investigator's opinion they are benefiting from treatment and they do not meet any other discontinuation criteria). Dose reduction to 250mg and subsequently 200mg is permitted following confirmation of toxicity.

Ding MA, PhD

This is a prospective, open-label, single arm, multi-centre interventional study to assess the clinical efficacy and safety of olaparib maintenance monotherapy and will be conducted in patients with platinum sensitive relapsed (PSR) high grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy

Eligible patients will be those with high grade (serous or endometrioid) epithelial ovarian cancer, primary peritoneal and/or fallopian tube cancer.

Patients must have completed 2 previous lines of platinum-based therapy (e.g., containing carboplatin or cisplatin) and platinum sensitive relapsed before entry to the study. Eligible patients must be in complete or partial response according to RECIST 1.1 criteria following the platinum-based chemotherapy prior to enrolment in the study.

BRCA (Breast Cancer Susceptibility genes) and HRR (Homologous Recombination Repair) mutation status should be determined through blood and/or tumour testing when patients are enrolled in this study.

Patients will be assigned olaparib tablets p.o. 300 mg twice daily. They should initiate olaparib treatment within 8 weeks after their last dose of platinum-containing chemotherapy (last dose is the day of the last infusion).

Patients must have clinical and objective radiological tumour assessments according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria at baseline and every 12 weeks relative to date of enrolment, until objective radiological disease progression as determined by the investigator. Patients could continue to receive olaparib for as long as determined by the investigator, until objective radiological disease progression or as long as in the investigator's opinion they are benefiting from treatment in relation to other clinical assessments and they do not meet any other discontinuation criteria. Once a patient has discontinued olaparib she will be managed as per local clinical practice but will remain in the study and data will be collected on subsequent treatments, progression, overall survival and safety.

Olaparib Tablets Maintenance Monotherapy Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy

An Open Label, Single Arm, Multicentre Study to Assess the Clinical Efficacy and Safety of Lynparza (Olaparib) Tablets Maintenance Monotherapy in Platinum Sensitive Relapsed Ovarian Cancer Patients Who Are in Complete or Partial Response Following Platinum Based Chemotherapy (L-MOCA)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

To assess the safety and tolerability of olaparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients

To assess the safety and tolerability of olaparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients.

To explore biomarkers in tumor tissues predictive of sensitivity/resistance to the treatment of olaparib.

To explore biomarkers in blood predictive of sensitivity/resistance to the treatment of olaparib.

Progression free survival (using investigator assessment) according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1) of olaparib tablets maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy

Progression free survival (using investigator assessment) according to modified Response Evaluation Criteria In Solid Tumours (RECIST 1.1) of olaparib tablets maintenance monotherapy in BRCA mutated platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy

Assessment of overall survival (OS) of olaparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Assessment of time from first dose date to second progression （investigator opinion of progression status）of olaparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Assessment of time to first subsequent therapy or death (TFST) of olaparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Assessment of time to second subsequent therapy or death (TSST) of olaparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Assessment of time to olaparib discontinuation or death (TDT) of olaparib maintenance monotherapy in platinum sensitive relapsed ovarian cancer patients who are in complete or partial response following platinum based chemotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.	NCT01844986	Newly Diagnosed Advanced Ovaria... FIGO Stage III-... BRCA Mutation Complete Respon... Partial Respons... First Line Plat...	Olaparib 300mg ...	18 Years - 130 Years	AstraZeneca
Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy	NCT01874353	Platinum Sensit... BRCA Mutated Relapsed Ovaria... Following Compl...	Olaparib 300mg ... Placebo to matc...	18 Years - 130 Years	AstraZeneca
Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.	NCT01844986	Newly Diagnosed Advanced Ovaria... FIGO Stage III-... BRCA Mutation Complete Respon... Partial Respons... First Line Plat...	Olaparib 300mg ...	18 Years - 130 Years	AstraZeneca
Olaparib Tablets Maintenance Monotherapy Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy	NCT03534453	Relapsed Ovaria... Following Compl... Platinum Sensit...	Olaparib 300mg ...	18 Years - 130 Years	AstraZeneca

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