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NCT01968213: ARIEL3

Phase 3 Study of Rucaparib as Switch Maintenance After Platinum in Relapsed High Grade Serous or Endometrioid Ovarian Cancer (ARIEL3)

Completed Phase 3 Results posted Last updated 9 June 2023
What this trial tests

Phase 3 trial testing Rucaparib in Ovarian Cancer in 564 participants. Completed in 7 July 2022.

Timeline
7 April 2014
Primary endpoint
1 April 2017
7 July 2022

Quick facts

Lead sponsorpharmaand GmbH
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment564
Start date7 April 2014
Primary completion1 April 2017
Estimated completion7 July 2022
Sites96 locations across France, Italy, New Zealand, Belgium, United Kingdom, Germany, Israel, Canada

Drugs / interventions tested

Conditions studied

Sponsor

pharmaand GmbH — full company profile →

Who can join

18 and older, female only, with Ovarian Cancer or Fallopian Tube Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · 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).

GroupValue95% CI
Rucaparib 600 mg Tablets10.88.3 – 11.4
Placebo Tablets5.45.3 – 5.5
Disease Progression According to RECIST v1.1, as Assessed by Independent Radiology Review (IRR), or Death From Any Cause (irrPFS) Secondary · 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.

To evaluate PFS by RECIST v1.1, as assessed by independent radiology review (IRR).

GroupValue95% CI
Rucaparib 600 mg Tablets13.711.0 – 19.1
Placebo Tablets5.45.1 – 5.5
Overall Survival (OS) Secondary · All patients were followed for survival up to approximately 8.2 years.

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.

GroupValue95% CI
Rucaparib 600 mg Tablets36.032.8 – 39.4
Placebo Tablets43.238.1 – 46.9
Time to a 4-point Decrease in the Disease-related Symptoms - Physical (DRS-P) Subscale of the FOSI-18 Secondary · 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.

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 o

GroupValue95% CI
Rucaparib 600 mg Tablets1.91.8 – 2.8
Placebo Tablets6.44.6 – 9.2
Time to an 8-point Decrease in the Total Score of the FOSI-18 Secondary · 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.

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 c

GroupValue95% CI
Rucaparib 600 mg Tablets2.92.7 – 3.7
Placebo Tablets10.89.2 – 17.5
Individual Model Parameter Estimates of Rucaparib and Covariates Identification Secondary · Study data collection occurred over approximately 7 months.

Concentration summary statistics

Cycle 2 Day 1
GroupValue95% CI
Rucaparib 600 mg Tablets1128± 95.42
Cycle 4 Day 1
GroupValue95% CI
Rucaparib 600 mg Tablets1136± 86.19
Cycle 7 Day 1
GroupValue95% CI
Rucaparib 600 mg Tablets1165± 78.53

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were reported from the date of first dose of study drug and until 28 days after last dose of study drug, approximately 8.2 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rucaparib 600 mg Tablets
Serious: 91/372 (24%)
Deaths: 9/372
Placebo Tablets
Serious: 20/189 (11%)
Deaths: 2/189

Serious adverse events (104 terms)

ReactionSystemRucaparib 600 mg TabletsPlacebo Tablets
AnaemiaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
PyrexiaGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
Myelodysplastic syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Small intestinal obstructionGastrointestinal disorders
Acute kidney injuryRenal and urinary disorders
Gastrointestinal painGastrointestinal disorders
Blood creatinine increasedInvestigations
DehydrationMetabolism and nutrition disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
SeizureNervous system disorders
Platelet count decreasedInvestigations
PancytopeniaBlood and lymphatic system disorders
Intestinal obstructionGastrointestinal disorders
General physical health deteriorationGeneral disorders
Incarcerated herniaGeneral disorders
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
Muscular weaknessMusculoskeletal and connective tissue disorders
Malignant melanomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal failureRenal and urinary disorders
Other adverse events (60 terms — click to expand)

ReactionSystemRucaparib 600 mg TabletsPlacebo Tablets
NauseaGastrointestinal disorders
FatigueGeneral disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Abdominal painGastrointestinal disorders
DysgeusiaNervous system disorders
Aspartate aminotransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
AstheniaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Photosensitivity reactionSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Blood creatinine increasedInvestigations
DizzinessNervous system disorders
DyspepsiaGastrointestinal disorders
InsomniaPsychiatric disorders
Abdominal pain upperGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
PruritusSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
Platelet count decreasedInvestigations
NeutropeniaBlood and lymphatic system disorders
Abdominal distensionGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
HypomagnesaemiaMetabolism and nutrition disorders
Oedema peripheralGeneral disorders
HypertensionVascular disorders
Urinary tract infectionInfections and infestations
Dry skinSkin and subcutaneous tissue disorders
NasopharyngitisInfections and infestations
Taste disorderNervous system disorders
AlopeciaSkin and subcutaneous tissue disorders
StomatitisGastrointestinal disorders

Most-reported serious reactions: Anaemia, Vomiting, Abdominal pain, Pyrexia, Febrile neutropenia, Constipation, Myelodysplastic syndrome, Small intestinal obstruction.

Data from ClinicalTrials.gov NCT01968213 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. PARP inhibitors: Synthetic lethality in the clinic.
    Lord CJ, Ashworth A. · · 2017 · cited 2241× · PMID 28302823 · DOI 10.1126/science.aam7344
  2. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial.
    Coleman RL, Oza AM, Lorusso D, Aghajanian C, et al · · 2017 · cited 1335× · PMID 28916367 · DOI 10.1016/s0140-6736(17)32440-6
  3. Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer.
    Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D'Andrea AD. · · 2015 · cited 733× · PMID 26463832 · DOI 10.1158/2159-8290.cd-15-0714
  4. Advances in ovarian cancer therapy.
    Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. · · 2018 · cited 417× · PMID 29249039 · DOI 10.1007/s00280-017-3501-8
  5. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45).
    Monk BJ, Parkinson C, Lim MC, O'Malley DM, et al · · 2022 · cited 300× · PMID 35658487 · DOI 10.1200/jco.22.01003
  6. Clinical and analytical validation of FoundationOne®CDx, a comprehensive genomic profiling assay for solid tumors.
    Milbury CA, Creeden J, Yip WK, Smith DL, et al · · 2022 · cited 292× · PMID 35294956 · DOI 10.1371/journal.pone.0264138
  7. DNA repair targeted therapy: The past or future of cancer treatment?
    Gavande NS, VanderVere-Carozza PS, Hinshaw HD, Jalal SI, et al · · 2016 · cited 279× · PMID 26896565 · DOI 10.1016/j.pharmthera.2016.02.003
  8. Poly (ADP-ribose) polymerase inhibitors: recent advances and future development.
    Scott CL, Swisher EM, Kaufmann SH. · · 2015 · cited 270× · PMID 25779564 · DOI 10.1200/jco.2014.58.8848

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01968213.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing