Clinical trial NCT02282020: 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
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
Keywords: BRCA, ovarian, platinum, chemotherapy,
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Myriad Genetic Laboratories, Inc.
name: Merck Sharp & Dohme LLC
First posted: 2014-11-04
Enrollment: 266
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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 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).

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
measure: Time From Randomisation to Second Progression (PFS2)
timeFrame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Overall Survival (OS)
timeFrame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death
timeFrame: RECIST and CA-125 follow-up assessments performed every 8 weeks (±1week), up to 48 weeks, then every 12 weeks (±1week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
measure: Time From Randomization To First Subsequent Therapy Or Death (TFST)
timeFrame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Time From Randomization To Second Subsequent Therapy Or Death (TSST)
timeFrame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Time From Randomization To Study Treatment Discontinuation Or Death (TDT)
timeFrame: Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Duration of Response (DoR)
timeFrame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
measure: Time to Response (TTR)
timeFrame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
measure: Mean Change From Baseline In Trial Outcome Index (TOI) Score
timeFrame: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
measure: Number of Participants Who Show an Improvement in TOI Score
timeFrame: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
measure: Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)
timeFrame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
measure: Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)
timeFrame: RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months)
measure: Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population
timeFrame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Overall Survival (OS) in BRCA Gene Population
timeFrame: Visits to occur every 12 weeks from the date of first progression, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population
timeFrame: Patients randomised to Olaparib administer their tablets orally at a dose of 300 mg twice daily and continue Olaparib until objective disease progression. Assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population
timeFrame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population
timeFrame: Anti-cancer treatments initiated post discontinuation of study treatment and investigator's opinion of response and date of progression recorded, assessed from date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
measure: Geometric Mean Plasma Concentration of Olaparib
timeFrame: Day 1, 1 hour post-dose and Day 29 pre-dose. DCO: 10Oct2018
measure: Number of Participants Who Experience at Least One Adverse Event (AE)
timeFrame: Safety Follow-up 30 days after last dose of IP, assessed from the date of first patient randomised to data cut off: 16Apr2021 (approx. 6 years 2 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Mobile
country: United States
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city: Sacramento
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state: California
city: San Francisco
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city: Albany
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state: New York
city: Mineola
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city: Springfield
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city: Abington
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state: Pennsylvania
city: Knoxville
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city: Nashville
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city: Bedford
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state: Texas
city: Houston
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city: Milwaukee
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state: Wisconsin
city: Berazategui
country: Argentina
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city: Caba
country: Argentina
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city: Ciudad de Buenos Aires
country: Argentina
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city: Cordoba
country: Argentina
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city: La Plata
country: Argentina
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city: San Miguel de Tucumán
country: Argentina
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city: Gent
country: Belgium
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city: Leuven
country: Belgium
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city: Ijui
country: Brazil
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city: Passo Fundo
country: Brazil
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country: Brazil
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city: São José do Rio Preto
country: Brazil
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country: Canada
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state: Ontario
city: Toronto
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state: Ontario
city: Montreal
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state: Quebec
city: Hradec Kralove
country: Czechia
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city: Ostrava-Poruba
country: Czechia
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city: Praha 2
country: Czechia
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city: Zlin
country: Czechia
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city: Budapest
country: Hungary
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city: Budapest
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city: Budapest
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city: Debrecen
country: Hungary
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city: Győr
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city: Miskolc
country: Hungary
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city: Afula
country: Israel
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city: Haifa
country: Israel
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city: Holon
country: Israel
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city: Jerusalem
country: Israel
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city: Jerusalem
country: Israel
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city: Petah Tikva
country: Israel
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city: Ramat Gan
country: Israel
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city: Rehovot
country: Israel
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city: Tel Hashomer
country: Israel
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city: Tel-Aviv
country: Israel
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city: Zerifin
country: Israel
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city: Meldola
country: Italy
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city: Messina
country: Italy
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city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Roma
country: Italy
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city: Roma
country: Italy
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
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city: Mexico
country: Mexico
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city: Mexico
country: Mexico
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city: Oaxaca
country: Mexico
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city: Gdańsk
country: Poland
facility: Research Site
city: Grzepnica
country: Poland
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city: Lublin
country: Poland
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city: Olsztyn
country: Poland
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city: Poznan
country: Poland
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city: Warszawa
country: Poland
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city: Łódź
country: Poland
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
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city: Gerona
country: Spain
facility: Research Site
city: Granada
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
affiliation: Harvard Medical School (HMS and HSDM)
name: Richard T Penson, Associate Prof. of Medicine
role: PRINCIPAL_INVESTIGATOR
References:
citation: Paulino E, Melo AC. SOLO 3 Trial: How Do the Results Fit in With Current Evidence? J Clin Oncol. 2020 Aug 10;38(23):2697-2698. doi: 10.1200/JCO.20.00576. Epub 2020 Jun 12. No abstract available.
citation: Penson RT, Lowe ES. Reply to E. Paulino et al. J Clin Oncol. 2020 Aug 10;38(23):2698. doi: 10.1200/JCO.20.01235. Epub 2020 Jun 12. No abstract available.
citation: Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidzinski M, Kim JW, Nam JH, Madry R, Hernandez C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. doi: 10.1200/JCO.19.02745. Epub 2020 Feb 19.