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. - Full Text View

Purpose

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	Intervention	Phase
Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity	Drug: OLAPARIB Drug: Single agent chemotherapy	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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.

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer ovarian cancer

MedlinePlus related topics: Cancer Genes and Gene Therapy Ovarian Cancer

Drug Information available for: Olaparib

Genetic and Rare Diseases Information Center resources: Ovarian Cancer

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Progression Free Survival (PFS) by blinded independent central review using Response Evaluation Criteria In Solid Tumours (RECIST) data [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ] [ Designated as safety issue: No ]
To determine the efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of PFS using blinded independent central review

Secondary Outcome Measures:

Efficacy of olaparib vs. physician's choice single agent chemotherapy by assessment of Overall Survival (OS) [ Time Frame: Up to 60 months ] [ Designated as safety issue: No ]
To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of OS
Efficacy in patients following platinum based chemotherapy by assessment of time from randomisation to second progression [ Time Frame: From date of randomization until the date of second documented progression or date of death from any cause, whichever came first, assessed up to 60 months ] [ Designated as safety issue: No ]
To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time from randomisation up to second progression
Efficacy in patients following platinum based chemotherapy by assessment of time to earliest progression by Cancer Antigen (CA-125) or death [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ] [ Designated as safety issue: No ]
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.
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: Up to 48 weeks ] [ Designated as safety issue: No ]
To determine the effects of olaparib vs. Physician's choice single agent chemotherapy by assessment of HRQoL as measured by TOI and FACT-O
Efficacy in patients with a deleterious or suspected deleterious variant in either of the BRCA genes by assessment of PFS. [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months ] [ Designated as safety issue: No ]
To determine 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).
Efficacy of olaparib by time to first subsequent therapy or death (TFST). [ Time Frame: From date of randomization until the date of first subsequent therapy or death assessed up to 60 months ] [ Designated as safety issue: No ]
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).
Efficacy of olaparib by time to second subsequent therapy or death (TSST). [ Time Frame: From date of randomization until the date of second subsequent therapy or death assessed up to 60 months ] [ Designated as safety issue: No ]
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).
Efficacy of olaparib by time from randomisation to study treatment discontinuation or death (TDT). [ Time Frame: From date of randomization until the date of study treatment discontinuation or death assessed up to 60 months ] [ Designated as safety issue: No ]
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).
Safety and tolerability of olaparib by assessment of the number of Adverse Events (AEs). [ Time Frame: Up to 30 days post-treatment for up to 60 months ] [ Designated as safety issue: Yes ]
To assess the safety and tolerability of olaparib maintenance monotherapy
Safety and tolerability of olaparib by review of laboratory parameters, ECG and vital signs [ Time Frame: Until study treatment discontinuation up to 60 months ] [ Designated as safety issue: Yes ]
To assess the safety and tolerability of olaparib maintenance monotherapy
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. ] [ Designated as safety issue: No ]
To determine the efficacy of olaparib vs. Physician's choice single agent chemotherapy by assessment of time to earliest progression by RECIST or death.


Estimated Enrollment:	411
Study Start Date:	February 2015
Estimated Study Completion Date:	December 2019
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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.

Eligibility


Ages Eligible for Study:	18 Years to 96 Years (Adult, Senior)
Genders Eligible for Study:	Female
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).

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: 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

Show 99 Study Locations

Sponsors and Collaborators

AstraZeneca

Myriad Genetic Laboratories, Inc.

Investigators


Principal Investigator:	Richard T Penson, Associate Prof. of Medicine	Harvard Medical School

More Information

Additional Information:

AstraZeneca Cancer Study Locator Service Phone 677 400 4656 Email astrazeneca@emergingmed.com This link exits the ClinicalTrials.gov site


Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT02282020 History of Changes
Other Study ID Numbers:	D0816C00010
Study First Received:	October 20, 2014
Last Updated:	September 21, 2016
Health Authority:	United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 26, 2016

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)