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

This study is currently recruiting participants.
Verified April 2014 by AstraZeneca
Sponsor:
Collaborators:
Gynecologic Oncology Group (GOG)
Myriad Genetics - BRACAnalysis test for FDA Premarket Approval (PMA)
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01844986
First received: April 30, 2013
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Newly Diagnosed
Advanced Ovarian Cancer
FIGO Stage III-IV
BRCA Mutation
Complete Response
Partial Response
First Line Platinum Chemotherapy
Drug: Olaparib 300mg tablets
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Progression Free Survival (PFS) by central review of RECIST data [ Time Frame: Radiologic scans performed at baseline then every ~12 weeks for ~2 years, then every ~24 weeks thereafter until objective radiological disease progression. Study data collection expected to last for ~7 years. ] [ Designated as safety issue: No ]
    To determine the efficacy by progression free survival (PFS) using blinded independent central review (BICR) 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.


Secondary Outcome Measures:
  • Efficacy in patients following First Line Platinum Based Chemotherapy by assessment of overall survival. [ Time Frame: Survival assessed every 4 weeks until treatment discontinues or for 2 years (whichever is earlier), then assessed every 12 weeks. Study data collection expected to last for ~7 years. ] [ Designated as safety issue: No ]
    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).

  • Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by TOI and FACT-O. [ Time Frame: Paper questionnaires completed by patient at baseline, Day 29 and then in line with RECIST assessments, until disease progression. Study data collection expected to last for ~7 years. ] [ Designated as safety issue: No ]
    To compare the effects of olaparib maintenance monotherapy compared to placebo on the rate of deterioration of 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.

  • Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of progression free survival. [ Time Frame: Radiologic scans performed at baseline then every ~12 weeks for ~2 years, then every ~24 weeks thereafter, until disease progression. Study data collection expected to last for ~7 years. ] [ Designated as safety issue: No ]
    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).

  • Safety and tolerability of olaparib by assessment of the number of AEs [ Time Frame: AEs collected from informed consent until post treatment 30-day follow-up period. Study data collection expected to last ~7 years. ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of olaparib maintenance monotherapy in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.

  • Efficacy in patients following First Line Platinum Based Chemotherapy by assessment of time to earliest progression by RECIST or Cancer Antigen-125 (CA-125). [ Time Frame: CA125 assessed every 4 weeks for ~2 years, then every 12 weeks. Radiologic scans performed every ~12 weeks for ~2 years, then every ~24 weeks until disease progression. Study data collection expected to last for ~7 years. ] [ Designated as safety issue: No ]
    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.

  • Efficacy in patients following First Line Platinum Based Chemotherapy by assessment of time from randomisation to second progression. [ Time Frame: Radiologic scans performed at baseline then every ~12 weeks for ~2 years, then every ~24 weeks until first progression. Then disease is assessed as per local clinical practice until 2nd progression. Study data collection expected to last for ~7 years. ] [ Designated as safety issue: No ]
    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 up to study completion at the latest.

  • Safety and tolerability of olaparib by assessment and review of laboratory parameters. [ Time Frame: Laboratory parameter assessments collected until study treatment discontinued. Study data collection expected to last ~7 years. ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of olaparib maintenance monotherapy in BRCA mutated high risk advanced ovarian cancer patients who are in clinical complete response or partial response following first line platinum based chemotherapy.

  • Efficacy of olaparib by time to first subsequent therapy or death (TFST). [ Time Frame: Time elapsed from randomisation to first subsequent therapy or death. Assessed at time of primary PFS analysis and at final OS analysis. Study data collection expected to last ~7 years. ] [ Designated as safety issue: No ]
    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).

  • Efficacy of olaparib by time to second subsequent therapy or death (TSST). [ Time Frame: Time elapsed from randomisation to second subsequent therapy or death. Assessed at time of primary PFS analysis and at final OS analysis. Study data collection expected to last ~7 years. ] [ Designated as safety issue: No ]
    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).

  • Efficacy of olaparib by time from randomisation to study treatment discontinuation or death (TDT). [ Time Frame: Time elapsed from randomisation to study treatment discontinuation or death. Assessed at time of primary PFS analysis and at final OS analysis. Study data collection expected to last ~7 years. ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 2500
Study Start Date: August 2013
Estimated Study Completion Date: January 2022
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olaparib tablets p.o. 300mg twice daily Drug: Olaparib 300mg tablets
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.
Placebo Comparator: Placebo tablets p.o. twice daily Drug: Olaparib 300mg tablets
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female patients with newly diagnosed, histologically confirmed, high risk advanced (FIGO stage III - IV) BRCA mutated high grade serous or high grade endometrioid ovarian cancer, primary peritoneal cancer and / or fallopian-tube cancer who have completed first line platinum based chemotherapy (intravenous or intraperitoneal).
  • Stage III patients must have had one attempt at optimal debulking surgery (upfront or interval debulking). Stage IV patients must have had either a biopsy and/or upfront or interval debulking surgery.
  • 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 completed first line platinum (e.g. carboplatin or cisplatin), containing therapy (intravenous or intraperitoneal) prior to randomisation:
  • Patients must have, in the opinion of the investigator, clinical complete response or partial response and have no clinical evidence of disease progression on the post treatment scan or rising CA-125 level, following completion of this chemotherapy course. Patients with stable disease on the post-treatment scan at completion of first line platinum-containing therapy are not eligible for the study.

Exclusion Criteria:

  • BRCA1 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, favor polymorphism" or "benign polymorphism" etc).
  • Patients with early stage disease (FIGO Stage I, IIA, IIB or IIC)
  • Stable disease or progressive disease on the post-treatment scan or clinical evidence of progression at the end of the patient's first line chemotherapy treatment.
  • Patients where more than one debulking surgery has been performed before randomisation to the study. (Patients who, at the time of diagnosis, are deemed to be unresectable and undergo only a biopsy or oophorectomy but then go on to receive chemotherapy and interval debulking surgery are eligible).
  • Patients who have previously been diagnosed and treated for earlier stage ovarian, fallopian tube or primary peritoneal cancer.
  • Patients who have previously received chemotherapy for any abdominal or pelvic tumour, including treatment for prior diagnosis at an earlier stage for their ovarian, fallopian tube or primary peritoneal cancer. (Patients who have received prior adjuvant chemotherapy for localised breast cancer may be eligible, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease).
  • Patients with synchronous primary endometrial cancer unless both of the following criteria are met: 1) stage <2 2) less than 60 years old at the time of diagnosis of endometrial cancer with stage IA or IB grade 1 or 2, or stage IA grade 3 endometrioid adenocarcinoma OR ≥ 60 years old at the time of diagnosis of endometrial cancer with Stage IA grade 1 or 2 endometrioid adenocarcinoma. Patients with serous or clear cell adenocarcinoma or carcinosarcoma of the endometrium are not eligible.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01844986

Contacts
Contact: Elizabeth Lowe ClinicalTrialTransparency@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator Service http://www.emergingmed.com/networks/AstraZeneca 001-877-400-4656 astrazeneca@emergingmed.com

  Show 179 Study Locations
Sponsors and Collaborators
AstraZeneca
Gynecologic Oncology Group (GOG)
Myriad Genetics - BRACAnalysis test for FDA Premarket Approval (PMA)
Investigators
Principal Investigator: Prof Paul DiSilvestro, MD Women & Infants Hospital, Providence, Rhode Island, USA
Principal Investigator: Prof Kathleen Moore, MD University of Oklahoma Health Sciences Center, Oklahoma City, USA
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01844986     History of Changes
Other Study ID Numbers: D0818C00001
Study First Received: April 30, 2013
Last Updated: April 4, 2014
Health Authority: Australia: National Health and Medical Research Council
Brazil: National Health Surveillance Agency
Canada: Canadian Institutes of Health Research
China: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: FSI Scientific Center of Expertise of Medical Application
Spain: Spanish Agency of Medicines
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
BRCA
Ovarian Cancer
Chemotherapy
PARP inhibitor
First Line
FIGO Stage III
FIGO Stage IV

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on April 17, 2014