Ovarian CancerPhase 3ARIEL3NCT01968213
Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3)
A Phase 3 study testing Rucaparib in people with Ovarian Cancer and Fallopian Tube Cancer, run by pharmaand GmbH at 96 sites in 11 countries.
Trial summary
Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- What is being tested?
- Rucaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 564 participants
- Where
- 96 sitesin 11 countries
- Study dates
- 7 Apr 2014to 7 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer.
- Received ≥2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial.
- Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen.
- Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response.
- For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response.
- Have sufficient archival tumor tissue for analysis.
Who cannot join
- History of prior cancer except for non-melanoma skin cancer, breast cancer curatively > 3 years ago, curatively treated solid tumor (>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer.
- Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible.
- Untreated or symptomatic central nervous system metastases.
- Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drug.
- Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.
Trial locations and contacts
96 sites in 11 countries.
96 sites in 11 countries
United States22 sites
Hope Women's Cancer Centers
Asheville, North Carolina, 28806
Johns Hopkins Universty
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Karmanos Cancer Institute - Wayne State University
Detroit, Michigan, 48201
Saint Jude Heritage Medical Center
Fullerton, California, 92835
Memorial Healthcare System
Hollywood, Florida, 33021
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Rocky Mountain Cancer Centers
Lakewood, Colorado, 80228
Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Florida Hospital
Orlando, Florida, 32804
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
University of California San Francisco (UCSF)
San Francisco, California, 94158
Coastal Integrative Cancer Care
San Luis Obispo, California, 93422
Central Coast Medical Oncology
Santa Maria, California, 93454
University of California Los Angeles (UCLA)
Santa Monica, California, 90404
University of Washington at Seattle
Seattle, Washington, 98109
Washington University School of Medicine - Division of Gynaecological Oncology
St Louis, Missouri, 63110
University of Arizona Cancer Center
Tucson, Arizona, 85704
United Kingdom12 sites
Belfast City Hospital
Belfast, Northern Ireland, BT9 7AB
Addenbrookes Hospital
Cambridge, CB20QQ
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, G120YN
St. James University Hospital
Leeds, West Yorkshire, LS97TF
Royal Marsden Hospital
London, England, SW3 6JJ
Barts Health NHS Trust
London, EC1M6BQ
Imperial College Healthcare NHS Trust
London, W120HS
Sarah Cannon Reserach Institute UK
London, W1G6AD
University College London
London, W1T4TJ
The Christie NHS Foundation Trust
Manchester, M204BX
Sir Bobby Robson Cancer trials research Centre, Northern Centre For Cancer Care
Newcastle upon Tyne, NE77DN
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
Spain10 sites
Centro Oncologico de Galica
A Coruña, 15009
Hospital Vall D'Hebron
Barcelona, 8035
Hospital Ramón y Cajal
Madrid, 28034
Hospital Universitario San Carlos
Madrid, 28040
Centro Integral Oncológico Clara Campal, Hospital de Madrid Norte-San Chinarro
Madrid, 28050
Hospital Regional Universitario Carlos Haya de Malaga
Málaga, 29011
Hospital Central de Asturias
Oviedo, Principality of Asturias, 33011
Hospital Universitario Virgen del Rocío
Seville, 41013
Instituto Valencia de Oncologia-Fundacion
Valencia, 46009
Hospital Clinico Universitario de Valencia
Valencia, 46010
France9 sites
Institute Bergonie
Bordeaux, 33076
Centre Francois Baclesse
Caen, Basse-Normandie, 14076
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69373
Centre Catherine de Sienne
Nantes, Pays de la Loire Region, 44202
Hospital Tenon
Paris, 75020
Hôpital Européen Georges-Pompidou
Paris, Île-de-France Region, 75908
Centre Hospitalier Lyon Sud
Pierre-Bénite, Auvergne-Rhône-Alpes, 69495
Institut Claudius Regaud
Toulouse, Midi-Pyrenees, 31052
Institut Gustave Roussy
Villejuif, Île-de-France Region, 94805
Canada8 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N4N2
Cross Cancer Institute
Edmonton, Alberta, T6G1Z2
Juravinski Cancer Centre
Hamilton, Ontario, L8V5C2
London Regional Cancer Centre
London, Ontario, N6A4L6
CHUM Centre Hospitalier de l'Université de Montréal
Montreal, Quebec, H2L4M1
Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H8L6
Centre Hospitalier Universitaire de Québec
Québec, G1R2J6
Princess Margaret Cancer Centre
Toronto, Ontario, M5G2M9
Italy8 sites
Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi
Bologna, 40138
Oncology Unit City Hospital degli Infermi
Faenza, Ravenna, 48018
Fondazione IRCCS National Cancer Institute
Milan, 20133
Instituto Europeo di Oncologia
Milan, 20141
Azienda Ospedaliero Universitaria Policlinico di Modena
Modena, 41124
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Naples, 80131
Arcispedale Santa Maria Nuova IRCCS
Reggio Emilia, Reggio Nella Emilia, 42100
Policlinico Universitario Agostino Gemelli
Roma, 00158
Australia7 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Royal Brisbane & Women's Hospital
Herston, Queensland, 4029
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009
Royal Melbourne Hospital
Parkville, Victoria, 3052
St John of God Hospital Subiaco
Subiaco, Western Australia, 608
Prince of Wales Hospital
Sydney, New South Wales, 2031
Westmead Hospital
Westmead, New South Wales, 2145
Germany7 sites
Klinikum Chemnitz gGmbH
Chemnitz, Saxony, 09116
Technische Universität Dresden
Dresden, Saxony, 01307
Universitätsklinikum Frankfurt
Frankfurt am Main, Hesse, 60596
Klinikum Ludwigsburg-Bietigheim gGmbH
Ludwigsburg, Baden-Wuerttembert, 71640
Rotkreuzklinikum Muenchen gGmbH
Munich, Bavaria, 80637
Klinikum Stuttgart
Stuttgart, Baden-Wurttemberg, 70174
Dr. Horst Schmidt Klinik, Klinik fuer Gynaekologie und Gyn. Onkologie
Wiesbaden, Hesse, 65199
Israel6 sites
Rambam Health Care Campus
Haifa, 31096
Lady Davis Carmel Medical Center
Haifa
Rabin Medical Center
Petah Tikva, 49100
Oncology Institute, Sheba Medical Center
Ramat Gan, 52621
Sourasky Medical Center
Tel Aviv, 64239
Assaf Harofeh M.C.
Ẕerifin, 70300
Belgium4 sites
AZ St Augustinus
Antwerp, 2610
UZ Gent
Ghent, B-9000
UZ Leuven
Leuven, 3000
Clinique Sainte-Elisabeth
Namur, 5000
New Zealand3 sites
Auckland City Hospital
Auckland, Grafton, 1023
Wellington Hospital
Newtown, Wellington Region, 6021
Palmsteron North Hospital
Palmerston North, Manawatu, 4442
About this study
Official title: A Study of Rucaparib as Switch Maintenance Following Platinum-Based Chemotherapy in Patients With Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer ( ARIEL3 )
Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.
Read the detailed description
Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). Clinical data have shown that ovarian cancer patients with and without evidence of a gBRCA mutation benefit from treatment with a PARP and that maintenance treatment with a PARP inhibitor following a response to platinum-based treatment increases PFS in patients with ovarian cancer. While patients with a BRCA mutation derived the most benefit, patients without evidence of a BRCA mutation also derived significant benefit.
Patients enrolled into this study will be stratified into 3 groups based on tumor HRD status. The purpose of this study is to identify which of these groups of patients will most likely benefit from treatment with rucaparib. It is anticipated that rucaparib will provide therapeutic benefit and increase PFS in patients with HRD associated with a BRCA gene mutation or other HR gene alteration.
- Conditions
- Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- Being tested
- Rucaparib, Placebo
- Keywords
- ARIEL3, ARIEL 3, platinum sensitive, PARP Inhibitor, rucaparib, homologous recombination, homologous recombination deficiency, CO-338, PF 01367338, AG 14699, platinum sensitive ovarian cancer, platinum sensitive fallopian tube cancer, platinum sensitive primary peritoneal cancer, platinum sensitive peritoneal cancer, gynecological cancer, Clovis, Clovis Oncology
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RucaparibDrug
Also called CO-338, PF 01367338, AG 14699
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
PlaceboDrug
Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole.
| Study group | Role | What they receive |
|---|---|---|
| Rucaparib | Experimental | Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole. Receives: Drug: Rucaparib |
| Placebo | Placebo comparator | Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease Progression According to RECIST Version 1.1, as Assessed by the Investigator, or Death From Any Cause (Investigator Progression Free Survival as Per invPFS)
Progression-free survival by Investigator (invPFS) is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever occurs first. Progressive disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
Measured: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 3 years.
Secondary outcomes (5)
Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS)
To evaluate PFS by RECIST v1.1, as assessed by independent radiology review (IRR).
Measured: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 8.2 years.
Overall Survival (OS)
Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive.
Measured: All patients were followed for survival up to approximately 8.2 years.
Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18
The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related symptoms and is based on numerical point scoring of symptoms. The DRS-P subscale of the questionnaire is specifically designed to assess physical symptoms of ovarian cancer and evaluate changes in the subscale point score in individual assessments over time. This study looked at the time to a 4-point reduction in subscale score as an indicator of improvement in disease-related physical symptoms on cancer therapy.
Measured: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
Time to an 8-point Decrease in the Total Score of the FOSI-18
The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) FACT-Ovarian Symptom Index (FOSI-18) is a questionnaire, for completion by patients, designed to assess the impact of cancer therapy on ovarian cancer-related physical, emotional and treatment-related symptoms, and is based on numerical point scoring of symptoms. The questionnaire is designed to evaluate changes in the total score in individual assessments over time. This study looked at the time to an 8-point reduction in the total score as an indicator of improvement in disease-related symptoms on cancer therapy.
Measured: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
Individual Model Parameter Estimates of Rucaparib and Covariates Identification
Concentration summary statistics
Measured: Study data collection occurred over approximately 7 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2013 (estimated)
- Study start7 Apr 2014
- Primary completion1 Apr 2017
- Study completion7 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 (6)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- 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
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 564 participants (actual)
Sponsor and investigators
- Lead sponsor
- pharmaand GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Foundation Medicine, Myriad Genetics, Inc.
- Responsible party
- Sponsor
- Investigators
- Heidi Giordano, Study director, Clovis Oncology, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01968213
- Sponsor's protocol ID
- CO-338-014
- Other IDs
- 2013-000518-39
- Acronym
- ARIEL3
- Status last verified
- Jun 2023
- First submitted
- 17 Oct 2013
- Last updated
- 9 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. doi: 10.1016/j.ygyno.2023.05.060. Epub 2023 May 30.
PubMed 37262961Green ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
PubMed 35397664Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
PubMed 35170751Colombo N, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Meunier J, Cameron T, Maloney L, Goble S, Bedel J, Ledermann JA, Coleman RL. The effect of age on efficacy, safety and patient-centered outcomes with rucaparib: A post hoc exploratory analysis of ARIEL3, a phase 3, randomized, maintenance study in patients with recurrent ovarian carcinoma. Gynecol Oncol. 2020 Oct;159(1):101-111. doi: 10.1016/j.ygyno.2020.05.045. Epub 2020 Aug 26.
PubMed 32861537Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. doi: 10.1016/S1470-2045(20)30061-9.
PubMed 32359490Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12.
PubMed 28916367
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Rucaparib as Switch Maintenance Following Platinum-Based Chemotherapy in Patients With Platinum-Sensitive, High-Grade Serous or Endometrioid Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer ( ARIEL3 )
- ClinicalTrials.gov ID
- NCT01968213
- Acronym / sponsor ID
- ARIEL3 / CO-338-014
- Conditions
- Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
- Keywords
- ARIEL3, ARIEL 3, platinum sensitive, PARP Inhibitor, rucaparib, homologous recombination, homologous recombination deficiency, CO-338
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 564 participants (actual)
- Lead sponsor
- pharmaand GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Foundation Medicine, Myriad Genetics, Inc.
- Study start
- 7 Apr 2014 (actual)
- Primary completion
- 1 Apr 2017 (actual)
- Study completion
- 7 Jul 2022 (actual)
- First posted
- 23 Oct 2013 (estimated)
- Results
- Posted 3 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients enrolled into this study will be stratified into 3 groups based on gene mutations identified in their tumor tissue. The purpose of this study is to evaluate patient response to maintenance treatment with rucaparib versus placebo. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples.
Detailed description
Rucaparib is an orally available, small molecule inhibitor of poly-adenosine diphosphate [ADP] ribose polymerase (PARP) being developed for treatment of ovarian cancer associated with homologous recombination (HR) DNA repair deficiency (HRD). Clinical data have shown that ovarian cancer patients with and without evidence of a gBRCA mutation benefit from treatment with a PARP and that maintenance treatment with a PARP inhibitor following a response to platinum-based treatment increases PFS in patients with ovarian cancer. While patients with a BRCA mutation derived the most benefit, patients without evidence of a BRCA mutation also derived significant benefit.
Patients enrolled into this study will be stratified into 3 groups based on tumor HRD status. The purpose of this study is to identify which of these groups of patients will most likely benefit from treatment with rucaparib. It is anticipated that rucaparib will provide therapeutic benefit and increase PFS in patients with HRD associated with a BRCA gene mutation or other HR gene alteration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rucaparib | Experimental | Drug: RucaparibOral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole. |
| Placebo | Placebo comparator | Drug: PlaceboOral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Confirmed diagnosis of high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer.
- Received ≥2 prior platinum-based treatment regimens including platinum based regimen that must have been administered immediately prior to maintenance therapy in this trial.
- Received no more than 1 non-platinum chemotherapy regimen. Prior hormonal therapy will not be counted as a non-platinum regimen.
- Must have had at least a 6-month disease-free period following prior treatment with the penultimate platinum-based chemotherapy and achieved a response.
- For the last chemotherapy course prior to study entry, patients must have received a platinum-based doublet chemotherapy regimen and have achieved a CR or PR (as defined by RECIST) and/or a GCIG CA-125 response.
Key exclusion criteria (5 listed)
- History of prior cancer except for non-melanoma skin cancer, breast cancer curatively > 3 years ago, curatively treated solid tumor (>5 years ago without evidence of recurrence), and synchronous endometrial cancer (Stage 1A) with ovarian cancer.
- Prior treatment with any PARP inhibitor, including rucaparib. Patients who received prior iniparib are eligible.
- Untreated or symptomatic central nervous system metastases.
- Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of study drug.
- Required drainage of ascites during the final 2 cycles of their last platinum-based regimen and/or during the period between the last dose of chemotherapy of that regimen and randomization to maintenance treatment in this study.
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 |
|---|---|---|
| RucaparibAlso: CO-338, PF 01367338, AG 14699Oral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole. | Drug | Rucaparib |
| PlaceboOral tablets administered twice daily with 8 oz (240 mL) of water on an empty stomach or with food; 28-day cycles of treatment. Doses should be taken as close to 12 hours apart as possible, preferably at the same times every day. Tablets should be swallowed whole. | Drug | Placebo |
Primary outcome
Disease Progression According to RECIST Version 1.1, as Assessed by the Investigator, or Death From Any Cause (Investigator Progression Free Survival as Per invPFS)
Time frame: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 3 years.
Progression-free survival by Investigator (invPFS) is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever occurs first. Progressive disease is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of measurable lesions, an unequivocal increase in existing non-measurable lesion(s), or the appearance of unequivocal new lesion(s).
5 secondary outcomes
Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS)
Time frame: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 8.2 years.
Overall Survival (OS)
Time frame: All patients were followed for survival up to approximately 8.2 years.
Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18
Time frame: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
Time to an 8-point Decrease in the Total Score of the FOSI-18
Time frame: Screening, Day 1 of each treatment cycle, Treatment Discontinuation visit, and 28-day Follow-up visit. Total follow-up was up to approximately 6.4 years.
Individual Model Parameter Estimates of Rucaparib and Covariates Identification
Time frame: Study data collection occurred over approximately 7 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37262961Peipert JD, Goble S, Isaacson J, Tang X, Wallace K, Coleman RL, Ledermann JA, Cella D. Patient-reported outcomes of maintenance rucaparib in patients with recurrent ovarian carcinoma in ARIEL3, a phase III, randomized, placebo-controlled trial. Gynecol Oncol. 2023 Aug;175:1-7. doi: 10.1016/j.ygyno.2023.05.060. Epub 2023 May 30.
- Derived from this study: PubMed 35397664Green ML, Ma SC, Goble S, Giordano H, Maloney L, Simmons AD, Beltman J, Harding TC, Xiao JJ. Population pharmacokinetics of rucaparib in patients with advanced ovarian cancer or other solid tumors. Cancer Chemother Pharmacol. 2022 May;89(5):671-682. doi: 10.1007/s00280-022-04413-7. Epub 2022 Apr 10.
- Derived from this study: PubMed 35170751Tattersall A, Ryan N, Wiggans AJ, Rogozinska E, Morrison J. Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer. Cochrane Database Syst Rev. 2022 Feb 16;2(2):CD007929. doi: 10.1002/14651858.CD007929.pub4.
- Derived from this study: PubMed 32861537Colombo N, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Meunier J, Cameron T, Maloney L, Goble S, Bedel J, Ledermann JA, Coleman RL. The effect of age on efficacy, safety and patient-centered outcomes with rucaparib: A post hoc exploratory analysis of ARIEL3, a phase 3, randomized, maintenance study in patients with recurrent ovarian carcinoma. Gynecol Oncol. 2020 Oct;159(1):101-111. doi: 10.1016/j.ygyno.2020.05.045. Epub 2020 Aug 26.
- Derived from this study: PubMed 32359490Ledermann JA, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp AR, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Banerjee S, Garcia-Donas J, Swisher EM, Cameron T, Maloney L, Goble S, Coleman RL. Rucaparib for patients with platinum-sensitive, recurrent ovarian carcinoma (ARIEL3): post-progression outcomes and updated safety results from a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020 May;21(5):710-722. doi: 10.1016/S1470-2045(20)30061-9.
- Derived from this study: PubMed 28916367Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12.
- ARIEL program websiteLink provided by the sponsor.
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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.
Heidi Giordano study director
Clovis Oncology, Inc.
96 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rucaparib in people with Ovarian Cancer and Fallopian Tube Cancer, run by pharmaand GmbH at 96 sites in 11 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 6 inclusion and 5 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 9 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 96 sites in United States, United Kingdom, Spain, France, Canada and 6 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. Some participants in this study may receive a placebo. 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 3 Aug 2018). 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?
Disease Progression According to RECIST Version 1.1, as Assessed by the Investigator, or Death From Any Cause (Investigator Progression Free Survival as Per invPFS) (time frame: Every 12 calendar weeks (within 7 days prior is permitted) after start of treatment until treatment discontinuation due to disease progression. Total follow-up was up to approximately 3 years.). 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 NCT01968213, which also lists 6 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 9 Jun 2023; AzTrials last refreshed its copy on 26 Oct 2026.