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Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments (SOLO3)

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ClinicalTrials.gov Identifier: NCT02282020
Recruitment Status : Recruiting
First Posted : November 4, 2014
Last Update Posted : May 30, 2018
Sponsor:
Collaborators:
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
Comparison of olaparib vs. physician's choice of single agent standard of care non-platinum based chemotherapy in patients with germline Breast Cancer susceptibility gene (gBRCA) mutated ovarian cancer who have progressed at least 6 months after the last platinum based chemotherapy. Patient should have received at least 2 prior lines of platinum based chemotherapy. The aim of the study is to assess the efficacy and safety of olaparib tablets.

Condition or disease Intervention/treatment Phase
Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity Drug: OLAPARIB Drug: Single agent chemotherapy Phase 3

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Detailed Description:
This open label, randomised, controlled, multi-centre study will assess the efficacy and safety of single agent olaparib vs. standard of care, based on physician's choice of single agent chemotherapy ( i.e paclitaxel, or topotecan, or pegylated liposomal doxorubicin, or gemcitabine) in platinum sensitive or partially platinum sensitive relapsed ovarian cancer patients who carry germline deleterious or suspected deleterious BRCA mutation and who have received at least 2 prior lines of platinum based chemotherapy. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Open Label, Randomised, Controlled, Multi-centre Study to Assess the Efficacy and Safety of Olaparib Monotherapy Versus Physician's Choice Single Agent Chemotherapy in the Treatment of Platinum Sensitive Relapsed Ovarian Cancer in Patients Carrying Germline BRCA1/2 Mutations.
Actual Study Start Date : February 6, 2015
Estimated Primary Completion Date : January 1, 2019
Estimated Study Completion Date : January 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Olaparib

Arm Intervention/treatment
Experimental: 1/OLAPARIB
olaparib 300mg oral tablets; twice daily
Drug: OLAPARIB
300 mg olaparib tablets taken orally twice daily. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria.

Active Comparator: 2/CHEMOTHERAPY
Physician's choice single agent chemotherapy
Drug: Single agent chemotherapy
Treatment of relapsed disease with single agent chemotherapy based on physician's choice of weekly paclitaxel, topotecan, pegylated liposomal doxorubicin, or gemcitabine. All patients should continue to receive study treatment until objective radiological disease progression as per RECIST 1.1 as assessed by the investigator or the patient experiences unacceptable toxicity or they meet any other discontinuation criteria




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Primary endpoint will be assessed at the time of the primary analysis: a minimum of 6 months after LSI, whichever is sooner ]
    To determine the efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of Objective Response Rate (ORR) using blinded independent central review (BICR).


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Time from randomization to death, at the time of the primary analysis (a minimum of 6 months after LSI, whichever is sooner), and at study completion, if different from the time of the primary analysis (estimated date - 01 Jan 2021). ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of OS

  2. PFS 2 - time from randomisation to second progression [ Time Frame: Time from randomization to death, at the time of the primary analysis (a minimum of 6 months after LSI, whichever is sooner), and at study completion, if different from the time of the primary analysis (estimated date - 01 Jan 2021). ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation up to second progression

  3. Time to earliest progression by RECIST 1.1 or Cancer Antigen (CA-125) or death [ Time Frame: Time from randomization to death, at the time of the primary analysis (a minimum of 6 months after LSI, whichever is sooner), and at study completion, if different from the time of the primary analysis (estimated date - 01 Jan 2021). ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time to earliest progression by CA-125 or death.

  4. Time to deterioration of Health-Related Quality of Life (HRQoL) as assessed by trial outcome index (TOI) and the Functional Assessment of Cancer Therapy - Ovarian (FACT-O) [ Time Frame: Questionnaire completed at baseline, Day 29 and then every 8 weeks for 48 weeks. ]
    To determine the effects of olaparib vs. Physician's choice single agent chemotherapy by assessment of HRQoL as measured by TOI and FACT-O

  5. Time to first subsequent therapy or death (TFST). [ Time Frame: Time from randomization to death, at the time of the primary analysis (a minimum of 6 months after LSI, whichever is sooner), and at study completion, if different from the time of the primary analysis (estimated date - 01 Jan 2021). ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation to first subsequent therapy or death (TFST).

  6. Time to second subsequent therapy or death (TSST). [ Time Frame: Time from randomization to death, at the time of the primary analysis (a minimum of 6 months after LSI, whichever is sooner), and at study completion, if different from the time of the primary analysis (estimated date - 01 Jan 2021). ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation to second subsequent therapy or death (TSST).

  7. Time from randomisation to study treatment discontinuation or death (TDT). [ Time Frame: Time from randomization to death, at the time of the primary analysis (a minimum of 6 months after LSI, whichever is sooner), and at study completion, if different from the time of the primary analysis (estimated date - 01 Jan 2021). ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation to study treatment discontinuation or death (TDT).

  8. Safety and tolerability of olaparib by assessment of the number of Adverse Events (AEs). [ Time Frame: Patients will be assessed until study treatment discontinuation, up until the end of the study estimated 01 Jan 2021. ]
    To assess the safety and tolerability of olaparib maintenance monotherapy

  9. Safety and tolerability of olaparib by review of laboratory parameters, ECG and vital signs [ Time Frame: Patients will be assessed until study treatment discontinuation, up until the end of the study estimated 01 Jan 2021. ]
    To assess the safety and tolerability of olaparib maintenance monotherapy

  10. Efficacy in patients following platinum based chemotherapy by assessment of time to earliest progression by RECIST or death [ Time Frame: Radiological assessments will be scheduled every 8 weeks (+/- 1 week) from randomisation for 48 weeks and every 12 weeks (+/- 1 week) thereafter until objective disease progression until study completion, estimated 01 Jan 2021 ]
    To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time to earliest progression by RECIST or death.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be ≥ 18 years of age
  • Patients with histologically diagnosed relapsed high grade serous ovarian cancer (including primary peritoneal and/or fallopian tube cancer) or high grade endometrioid cancer. Patients are eligible to undergo BRCA testing even if they have not yet had recurrence or progression of disease >6 months (>/=183 days) after completion of their last platinum therapy.
  • Documented germline mutation in Breast Cancer susceptibility genes: BRCA1 and/or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
  • At least one lesion that can be accurately assessed at baseline by CT/MRI and is suitable for repeated assessment.
  • Patients must have received at least 2 prior platinum based lines of chemotherapy - Patients must be partially platinum sensitive or platinum sensitive
  • Patients must be suitable to start treatment with single agent chemotherapy based on physician's choice
  • Patients must have normal organ and bone marrow function measured within 28 days of randomisation,
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Patients must have a life expectancy ≥ 16 weeks
  • Formalin fixed, paraffin embedded tumour sample from the primary or recurrent cancer must be available for central testing.

Exclusion Criteria:

  • BRCA 1 and/or BRCA2 mutations that are considered to be non detrimental
  • Exposure to any investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
  • Any previous treatment with a Polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor, including olaparib.
  • Patients who have platinum resistant or refractory disease
  • Patients receiving any systemic chemotherapy within 3 weeks prior to first dose of study treatment
  • Previous single agent exposure to the selected chemotherapy regimen for randomisation. - Prior malignancy in the last 5 years, unless curatively treated and recurrence free (few exceptions apply).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02282020


Contacts
Contact: AstraZeneca Clinical Study Information Center, Senior Medical Lead 1-877-240-9479 information.center@astrazeneca.com
Contact: Elizabeth S Lowe, Dr Elizabeth.Lowe@astrazeneca.com

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Sponsors and Collaborators
AstraZeneca
Myriad Genetic Laboratories, Inc.
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Richard T Penson, Associate Prof. of Medicine Harvard Medical School

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02282020     History of Changes
Other Study ID Numbers: D0816C00010
First Posted: November 4, 2014    Key Record Dates
Last Update Posted: May 30, 2018
Last Verified: May 2018

Keywords provided by AstraZeneca:
BRCA, ovarian, platinum, chemotherapy,

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
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents