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

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ClinicalTrials.gov Identifier: NCT01844986
Recruitment Status : Active, not recruiting
First Posted : May 3, 2013
Results First Posted : July 9, 2019
Last Update Posted : July 9, 2019
Sponsor:
Collaborators:
Gynecologic Oncology Group (GOG)
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE April 30, 2013
First Posted Date  ICMJE May 3, 2013
Results First Submitted Date  ICMJE May 9, 2019
Results First Posted Date  ICMJE July 9, 2019
Last Update Posted Date July 9, 2019
Actual Study Start Date  ICMJE August 26, 2013
Actual Primary Completion Date May 17, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
Progression Free Survival (PFS) Using Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumours (RECIST 1.1) [ Time Frame: Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks thereafter until objective radiological disease progression. Analysis of data assessed up to a maximum of 54 months. ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 1, 2013)
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. ]
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.
Change History Complete list of historical versions of study NCT01844986 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2019)
  • Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Overall Survival [ Time Frame: Survival assessed every 4 weeks until treatment discontinues, then every 12 weeks (analysis of data assessed up to a maximum of 54 months). Analysed at the PFS analysis and a further analysis of OS will be performed at approximately 60% maturity. ]
    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)
  • 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 [ Time Frame: CA-125 performed at baseline then every 4 weeks. Radiologic scans performed at baseline then every 12 weeks up to 156 weeks, then every 24 weeks until objective radiological disease progression. Analysis of data assessed up to a maximum of 54 months. ]
    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)
  • Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Second Progression [ Time Frame: Following first progression disease then assessed per local practice every 12 weeks until second progression. Analysis of data assessed up to a maximum of 54 months. ]
    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)
  • 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) [ Time Frame: Questionnaires will be given to the patient at baseline, at Day 29 and then every 12 weeks for 156 weeks, then every 24 weeks or until the data cut off for the PFS analysis, change in TOI over 24 months reported ]
    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.
  • Efficacy in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to First Subsequent Therapy or Death (TFST) [ Time Frame: Assessed every 12 weeks following treatment discontinuation. Analysis of data assessed up to a maximum of 54 months. A further analysis of TFST will be performed at approximately 60% OS maturity. ]
    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 in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time to Second Subsequent Therapy or Death (TSST) [ Time Frame: Assessed every 12 weeks following treatment discontinuation. Analysis of data assessed up to a maximum of 54 months. A further analysis of TSST will be performed at approximately 60% OS maturity. ]
    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 in Patients Following First Line Platinum Based Chemotherapy by Assessment of Time From Randomization to Study Treatment Discontinuation or Death (TDT) [ Time Frame: Time elapsed from randomization to study treatment discontinuation or death. Analysis of data assessed up to a maximum of 54 months. A further analysis of TDT may be performed at approximately 60% OS maturity. ]
    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).
  • Efficacy in Patients With a Deleterious or Suspected Deleterious Variant in Either of the BRCA Genes by Assessment of PFS [ Time Frame: Radiologic scans performed at baseline then every 12 weeks for the first 156 weeks, then every 24 weeks thereafter, assessed until disease progression. Analysis of data assessed up to a maximum of 54 months. ]
    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)
Original Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2013)
  • 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. ]
    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. ]
    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. ]
    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. [ Time Frame: AEs collected from informed consent until post treatment 30-day follow-up period. Laboratory parameter assessments collected until study treatment discontinued. Study data collection expected to last ~7 years. ]
    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. ]
    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. ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy.
Official Title  ICMJE 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.
Brief Summary Olaparib Monotherapy in Patients with BRCA Mutated Ovarian Cancer following First Line Platinum Based Chemotherapy.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Newly Diagnosed
  • Advanced Ovarian Cancer
  • FIGO Stage III-IV
  • BRCA Mutation
  • Complete Response
  • Partial Response
  • First Line Platinum Chemotherapy
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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
    Intervention: Drug: Olaparib 300mg tablets
  • 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
    Intervention: Drug: Olaparib 300mg tablets
Publications * Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018 Dec 27;379(26):2495-2505. doi: 10.1056/NEJMoa1810858. Epub 2018 Oct 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 21, 2019)
450
Original Estimated Enrollment  ICMJE
 (submitted: May 1, 2013)
344
Estimated Study Completion Date  ICMJE August 5, 2025
Actual Primary Completion Date May 17, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Canada,   China,   France,   Israel,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Russian Federation,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01844986
Other Study ID Numbers  ICMJE D0818C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE
  • Gynecologic Oncology Group (GOG)
  • Myriad Genetic Laboratories, Inc.
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
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
PRS Account AstraZeneca
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP