Relapsed Ovarian Cancer, BRCA Mutation, Platinum SensitivityPhase 3SOLO3NCT02282020
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
A Phase 3 study testing OLAPARIB and Single agent chemotherapy in people with Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity, run by AstraZeneca at 94 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years, women only
- Conditions the study is for
- Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
- What is being tested?
- OLAPARIB and Single agent chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 266 participants
- Where
- 94 sitesin 13 countries
- Study dates
- 6 Feb 2015to 19 Jul 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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.
Who cannot join
- 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).
Trial locations and contacts
94 sites in 13 countries.
94 sites in 13 countries
United States22 sites
Research Site
Abington, Pennsylvania, 19001
Research Site
Albany, New York, 12208
Research Site
Aurora, Colorado, 80045
Research Site
Bedford, Texas, 76022
Research Site
Birmingham, Alabama, 35233
Research Site
Chapel Hill, North Carolina, 27599
Research Site
Columbus, Ohio, 43210
Research Site
Covington, Louisiana, 70433
Research Site
Detroit, Michigan, 48201
Research Site
Fort Gordon, Georgia, 30905
Research Site
Hartford, Connecticut, 06106
Research Site
Houston, Texas, 77030
Research Site
Knoxville, Tennessee, 37920
Research Site
Littleton, Colorado, 80120
Research Site
Milwaukee, Wisconsin, 53226
Research Site
Mineola, New York, 11501
Research Site
Mobile, Alabama, 36604
Research Site
Nashville, Tennessee, 37232
Research Site
Sacramento, California, 95817
Research Site
San Francisco, California, 94118
Research Site
Springfield, Oregon, 97477
Research Site
Towson, Maryland, 21204
Israel11 sites
Research Site
Afula, 18101
Research Site
Haifa, 31096
Research Site
Holon, 58100
Research Site
Jerusalem, 9103102
Research Site
Jerusalem, 91120
Research Site
Petah Tikva, 4941492
Research Site
Ramat Gan, 52621
Research Site
Rehovot, 7661041
Research Site
Tel Aviv, 6423906
Research Site
Tel HaShomer, 52621
Research Site
Tsrifin, 70300
Brazil8 sites
Research Site
Ijuí, 98700-000
Research Site
Passo Fundo, 99010 260
Research Site
Porto Alegre, 90035-003
Research Site
Porto Alegre, 90610-000
Research Site
Rio de Janeiro, 22793-080
Research Site
São José do Rio Preto, 15090-000
Research Site
São Paulo, 01246-000
Research Site
São Paulo, 01317-000
Italy8 sites
Research Site
Meldola, 47014
Research Site
Messina, 98158
Research Site
Milan, 20132
Research Site
Milan, 20133
Research Site
Milan, 20141
Research Site
Naples, 80131
Research Site
Roma, 00144
Research Site
Roma, 00168
Spain8 sites
Research Site
Barcelona, 08035
Research Site
Barcelona, 08036
Research Site
Barcelona, 08907
Research Site
Córdoba, 14004
Research Site
Girona, 17007
Research Site
Granada, 18014
Research Site
Madrid, 28040
Research Site
Madrid, 28050
Poland7 sites
Research Site
Gdansk, 80-219
Research Site
Grzepnica, 72-003
Research Site
Lodz, 93-513
Research Site
Lublin, 20-090
Research Site
Olsztyn, 10-561
Research Site
Poznan, 60-569
Research Site
Warsaw, 02-781
Argentina6 sites
Research Site
Berazategui, B1884BBF
Research Site
CABA, C1280AEB
Research Site
Ciudad de Buenos Aires, C1180AAX
Research Site
Córdoba, 5000
Research Site
La Plata, B1897GPD
Research Site
San Miguel de Tucumán, T4000IAK
Hungary6 sites
Research Site
Budapest, 1088
Research Site
Budapest, 1115
Research Site
Budapest, 1122
Research Site
Debrecen, 4032
Research Site
Győr, 9024
Research Site
Miskolc, 3526
South Korea6 sites
Research Site
Goyang-si, 10408
Research Site
Seoul, 03080
Research Site
Seoul, 06273
Research Site
Seoul, 06351
Research Site
Seoul, 138-736
Research Site
Seoul, 139-706
Czechia4 sites
Research Site
Hradec Králové, 500 05
Research Site
Ostrava-Poruba, 708 52
Research Site
Prague, 128 08
Research Site
Zlín, 762 75
Canada3 sites
Research Site
Montreal, Quebec, H2L 4M1
Research Site
Toronto, Ontario, M4N 3M5
Research Site
Toronto, Ontario, M5G 1X6
Mexico3 sites
Research Site
México, 07760
Research Site
México, 6760
Research Site
Oaxaca City, 68000
About this study
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.
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.
Read the 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.
- Being tested
- OLAPARIB, Single agent chemotherapy
- Keywords
- BRCA, ovarian, platinum, chemotherapy,
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OLAPARIBDrug
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.
Single agent chemotherapyDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 1/OLAPARIB | Experimental | olaparib 300mg oral tablets; twice daily Receives: Drug: OLAPARIB |
| 2/CHEMOTHERAPY | Active comparator | Physician's choice single agent chemotherapy Receives: Drug: Single agent chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
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)
Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment
ORR is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.
Measured: 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 (20)
Progression Free Survival (PFS)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by progression free survival (PFS) using BICR assessment according to RECIST 1.1 criteria
PFS is defined as the time from randomization until the date of objective radiological disease progression according to RECIST 1.1 or death (by any cause in the absence of disease progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to disease progression (i.e., date of RECIST progression/death or censoring - date of randomization +1).
Measured: 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)
Time From Randomisation to Second Progression (PFS2)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by second progression (PFS2).
Time from randomization to PFS2 is defined as the time from the date of randomization to the earliest of the progression events subsequent to first progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could involve objective radiological, clinical, cancer antigen-125 (CA-125) progression or death. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG) criteria.
Measured: 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)
Overall Survival (OS)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by overall survival (OS).
Overall survival is defined as the time from the date of randomisation until death due to any cause.
Measured: 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)
Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time to earliest progression by RECIST 1.1 or CA-125 or death.
Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment. CA-125 progression was assessed per Gynecological Cancer Intergroup (GCIG).
Measured: 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)
Time From Randomization To First Subsequent Therapy Or Death (TFST)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time from randomisation to first subsequent therapy or death (TFST)
TFST is defined as the time from the date of randomisation to the earlier of first subsequent chemotherapy start date or death.
Anti-cancer treatments include chemotherapy and targeted agents.
Measured: 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)
Time From Randomization To Second Subsequent Therapy Or Death (TSST)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time from randomisation to second subsequent therapy or death (TSST)
TSST was defined as the time from the date of randomisation to the earlier of second subsequent chemotherapy start date or death.
Anti-cancer treatments include chemotherapy and targeted agents.
Measured: 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)
Time From Randomization To Study Treatment Discontinuation Or Death (TDT)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time to study treatment discontinuation or death (TDT)
TDT was defined as the time from randomization to the earlier of the date of study treatment discontinuation or death.
Measured: 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)
Duration of Response (DoR)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by duration of response (DoR) by BICR using RECIST 1.1 criteria for evaluable patients.
Duration of response is the time from the first documentation of complete response (CR) or partial response (PR) until the date of progression or death, or the last evaluable RECIST assessment for participants that do not progress or progress after 2 missed assessments. Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used to assess participant response to treatment.
Measured: 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)
Time to Response (TTR)
To determine the efficacy of single agent olaparib vs. physician's choice single agent chemotherapy by time to response (TTR) by BICR using RECIST 1.1 criteria for evaluable patients.
TTR was defined as the time from randomization until the date of first documented response by Blinded independent central review (BICR) assessment.
Measured: 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)
Mean Change From Baseline In Trial Outcome Index (TOI) Score
To compare the efficacy of single agent olaparib versus physician's choice single agent chemotherapy on the Health-related Quality of Life (HRQoL) as measured by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)
The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher HRQoL. A negative change in score from baseline indicated a worsening in symptoms.
Measured: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
Number of Participants Who Show an Improvement in TOI Score
To compare the efficacy of single agent olaparib versus physician's choice single agent chemotherapy on the Health-related Quality of Life (HRQoL) as measured by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy - Ovarian (FACT-O)
The TOI score was derived from the sum of the scores of the 25 items included in the physical well-being (7 items), functional well-being (7 items), and additional concerns ovarian cancer subscale (11 items) of the FACT-O questionnaire Version 4. TOI score ranges from 0 to 100, a higher score indicates a higher health-related quality of life (HRQoL). A change in at least 10 points was considered clinically relevant.
Measured: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)
BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
The number of participants with complete or partial response per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Partial response is declared when there is a decrease in sum of target disease ≥ 30%. Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.
Measured: 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)
Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)
BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Progressive disease was defined as at least 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Measured: 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)
Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population
BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Measured: 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)
Overall Survival (OS) in BRCA Gene Population
BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
OS in BRCA gene population was measured by the number of participants who died due to any cause.
Measured: 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)
Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population
BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Measured: 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)
Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population
BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Anti-cancer treatments include chemotherapy and targeted agents.
Measured: 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)
Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population
BRCA gene population includes participants 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 (eg, gene sequencing and large rearrangement analysis).
Anti-cancer treatments include chemotherapy and targeted agents.
Measured: 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)
Geometric Mean Plasma Concentration of Olaparib
Summary of plasma concentrations (ug/mL) of olaparib
Measured: Day 1, 1 hour post-dose and Day 29 pre-dose. DCO: 10Oct2018
Number of Participants Who Experience at Least One Adverse Event (AE)
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2014 (estimated)
- Study start6 Feb 2015
- Primary completion10 Oct 2018
- Study completion19 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Relapsed Ovarian Cancer, BRCA Mutation, Platinum SensitivityStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 266 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Myriad Genetic Laboratories, Inc., Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Richard T Penson, Associate Prof. of Medicine, Principal investigator, Harvard Medical School (HMS and HSDM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02282020
- Sponsor's protocol ID
- D0816C00010
- Acronym
- SOLO3
- Status last verified
- Jul 2022
- First submitted
- 20 Oct 2014
- Last updated
- 26 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
- Expanded access
- Available
Publications
Scambia G, Villalobos Valencia R, Colombo N, Cibula D, Leath CA 3rd, Bidzinski M, Kim JW, Nam JH, Madry R, Hernandez C, Mora PAR, Ryu SY, Ah-See ML, Lowe ES, Lukashchuk N, Carter D, Penson RT. Olaparib as Treatment Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer: Phase III SOLO3 Study Final Overall Survival Results. J Clin Oncol. 2025 Apr 20;43(12):1408-1416. doi: 10.1200/JCO.24.00933. Epub 2024 Dec 12.
PubMed 39668137Paulino 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.
PubMed 32530768Penson 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.
PubMed 32530766Penson 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.
PubMed 32073956
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02282020
- Acronym / sponsor ID
- SOLO3 / D0816C00010
- Keywords
- BRCA, ovarian, platinum, chemotherapy,
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 266 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Myriad Genetic Laboratories, Inc., Merck Sharp & Dohme LLC
- Study start
- 6 Feb 2015 (actual)
- Primary completion
- 10 Oct 2018 (actual)
- Study completion
- 19 Jul 2022 (actual)
- First posted
- 4 Nov 2014 (estimated)
- Results
- Posted 2 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1/OLAPARIB | Experimental | Drug: OLAPARIBolaparib 300mg oral tablets; twice daily |
| 2/CHEMOTHERAPY | Active comparator | Drug: Single agent chemotherapyPhysician's choice single agent chemotherapy |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OLAPARIB300 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. | Drug | 1/OLAPARIB |
| Single agent chemotherapyTreatment 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 | Drug | 2/CHEMOTHERAPY |
Primary outcome
Objective Response Rate (ORR)
Time frame: 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)
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) Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria was used by a Blinded Independent Central Review (BICR) to assess participant response to treatment ORR is the number of participants with Complete Response (CR) or Partial Response (PR) in the Measurable Disease Analysis Set (MDAS). Complete response is declared when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each. Partial response is declared when there is a decrease in sum of diameters of target lesions ≥ 30%.
20 secondary outcomes
Progression Free Survival (PFS)
Time frame: 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)
Time From Randomisation to Second Progression (PFS2)
Time frame: 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)
Overall Survival (OS)
Time frame: 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)
Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death
Time frame: 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)
Time From Randomization To First Subsequent Therapy Or Death (TFST)
Time frame: 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)
Time From Randomization To Second Subsequent Therapy Or Death (TSST)
Time frame: 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)
Time From Randomization To Study Treatment Discontinuation Or Death (TDT)
Time frame: 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)
Duration of Response (DoR)
Time frame: 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)
Time to Response (TTR)
Time frame: 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)
Mean Change From Baseline In Trial Outcome Index (TOI) Score
Time frame: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
Number of Participants Who Show an Improvement in TOI Score
Time frame: Baseline (Day 1) to Week 48 (±1 week). DCO: 10Oct2018
Objective Response Rate (ORR) in Breast Cancer Susceptibility (BRCA) Gene Population by Blinded Independent Central Review (BICR)
Time frame: 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)
Number of Participants Who Experienced Disease Progression or Death in BRCA Gene Population by Blinded Independent Central Review (BICR)
Time frame: 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)
Number of Participants Who Experienced Second Progression or Death (PFS2) in BRCA Gene Population
Time frame: 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)
Overall Survival (OS) in BRCA Gene Population
Time frame: 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)
Number of Participants Who Discontinued Study Treatment or Died in BRCA Gene Population
Time frame: 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)
Number of Participants Who Received Subsequent Chemotherapy or Died in BRCA Gene Population
Time frame: 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)
Number of Participants Who Received Second Subsequent Chemotherapy or Died in BRCA Gene Population
Time frame: 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)
Geometric Mean Plasma Concentration of Olaparib
Time frame: Day 1, 1 hour post-dose and Day 29 pre-dose. DCO: 10Oct2018
Number of Participants Who Experience at Least One Adverse Event (AE)
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39668137Scambia G, Villalobos Valencia R, Colombo N, Cibula D, Leath CA 3rd, Bidzinski M, Kim JW, Nam JH, Madry R, Hernandez C, Mora PAR, Ryu SY, Ah-See ML, Lowe ES, Lukashchuk N, Carter D, Penson RT. Olaparib as Treatment Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer: Phase III SOLO3 Study Final Overall Survival Results. J Clin Oncol. 2025 Apr 20;43(12):1408-1416. doi: 10.1200/JCO.24.00933. Epub 2024 Dec 12.
- Derived from this study: PubMed 32530768Paulino 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.
- Derived from this study: PubMed 32530766Penson 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.
- Derived from this study: PubMed 32073956Penson 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.
- AstraZeneca Cancer Study Locator Service Phone 677 400 4656 Email astrazeneca@emergingmed.comLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- CSR Synopsis addendumLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Related trials for Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity
Active, not recruitingPhase 3
Olaparib Treatment in BRCA Mutated Ovarian Cancer Patients After Complete or Partial Response to Platinum Chemotherapy
Platinum Sensitive, BRCA Mutated
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard T Penson, Associate Prof. of Medicine principal investigator
Harvard Medical School (HMS and HSDM)
94 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing OLAPARIB and Single agent chemotherapy in people with Relapsed Ovarian Cancer, BRCA Mutation, Platinum Sensitivity, run by AstraZeneca at 94 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 94 sites in United States, Israel, Brazil, Italy, Spain and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02282020, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2022.