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Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy. (SOLO-1)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Gynecologic Oncology Group (GOG)
Myriad Genetic Laboratories, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01844986
First received: April 30, 2013
Last updated: November 24, 2016
Last verified: November 2016
  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 review of investigator-reported RECIST data [ Time Frame: Radiologic scans performed at baseline then every ~12 weeks up to 3 years (156 weeks) and every ~24 weeks thereafter until objective radiological disease progression. Study data collection expected to last for ~10 years. ] [ Designated as safety issue: No ]
    To determine the efficacy by progression free survival (PFS) using investigator assessment of scans 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 up to 3 years (whichever is earlier), then assessed every 12 weeks. Study data collection expected to last for ~10 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).

  • Change from baseline in Health-Related Quality of Life (HRQoL) as assessed by the individual domains of the trial outcome index (TOI) of the Functional Assessment of Cancer therapy - Ovarian (FACT-O) [ Time Frame: Questionnaires completed by patient at baseline, Day 29, every 12 weeks until week 156 and then 24 weeks or until the data cut off for the primary analysis, whichever comes first. Study data collection expected to last for ~10 years. ] [ Designated as safety issue: No ]
    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.

  • 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 every ~12 weeks for up to 3 years and every ~24 weeks thereafter, until disease progression. Study data collection expected to last for ~10 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 ~10 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 up to 3 years, then every 12 weeks. Radiologic scans performed every ~12 weeks for up to 3 years, then every ~24 weeks until disease progression. Study data collection expected to last for ~10 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 up to 3 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~10 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 ~10 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 ~10 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 ~10 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 ~10 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: 397
Study Start Date: August 2013
Estimated Study Completion Date: March 2023
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Olaparib tablets p.o. 300mg twice daily
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
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
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
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 to 130 Years   (Adult, Senior)
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.
  • Patients must be randomized within 8 weeks of their last dose of chemotherapy

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01844986

  Show 177 Study Locations
Sponsors and Collaborators
AstraZeneca
Gynecologic Oncology Group (GOG)
Myriad Genetic Laboratories, Inc.
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

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01844986     History of Changes
Other Study ID Numbers: D0818C00001 
Study First Received: April 30, 2013
Last Updated: November 24, 2016
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
Polystyrene sulfonic acid
Olaparib
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 08, 2016