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NCT01891344: ARIEL2

A Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)

Completed Phase 2 Results posted Last updated 12 June 2023
What this trial tests

Phase 2 trial testing Oral rucaparib in Ovarian Cancer in 491 participants. Completed in 28 September 2021.

Timeline
30 October 2013
Primary endpoint
5 November 2019
28 September 2021

Quick facts

Lead sponsorpharmaand GmbH
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment491
Start date30 October 2013
Primary completion5 November 2019
Estimated completion28 September 2021
Sites75 locations across France, United Kingdom, Canada, Australia, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

pharmaand GmbH — full company profile →

Who can join

18 and older, female only, with Ovarian Cancer or Epithelial Ovarian 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.

Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study) Primary · Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

GroupValue95% CI
Part 1: tBRCA388273 – 448
Part 1: Non-tBRCA LOH+174158 – 231
Part 1: Non-tBRCA LOH-160110 – 188
Part 1: Non-tBRCA LOH Unknown22355 – 499
Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) Primary · Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

GroupValue95% CI
Part 2: tBRCA31.021.3 – 42.0
Part 2: Non-tBRCA LOH+6.82.3 – 15.3
Part 2: Non-tBRCA LOH-5.62.1 – 11.8
Part 2: Non-tBRCA LOH Unknown13.02.8 – 33.6
Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study) Secondary · Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or PR on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

GroupValue95% CI
Part 1: tBRCA80.064.4 – 90.9
Part 1: Non-tBRCA LOH+28.018.7 – 39.1
Part 1: Non-tBRCA LOH-10.04.1 – 19.5
Part 1: Non-tBRCA LOH Unknown33.39.9 – 65.1
Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria Secondary · Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A response to CA-125 has occurred if there is at least a 50% decrease

GroupValue95% CI
Part 1: tBRCA87.573.2 – 95.8
Part 1: Non-tBRCA LOH+46.335.3 – 57.7
Part 1: Non-tBRCA LOH-21.412.5 – 32.9
Part 1: Non-tBRCA LOH Unknown50.021.1 – 78.9
Part 2: tBRCA54.843.5 – 65.7
Part 2: Non-tBRCA LOH+12.35.8 – 22.1
Part 2: Non-tBRCA LOH-13.17.3 – 21.0
Part 2: Non-tBRCA LOH Unknown30.413.2 – 52.9
Duration of Response Per RECIST v1.1 Secondary · Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is at least

GroupValue95% CI
Part 1: tBRCA281194 – 393
Part 1: Non-tBRCA LOH+329174 – 451
Part 1: Non-tBRCA LOH-169141 – 260
Part 1: Non-tBRCA LOH Unknown225100 – 1454
Part 2: tBRCA176169 – 312
Part 2: Non-tBRCA LOH+282111 – NA
Part 2: Non-tBRCA LOH-314169 – NA
Part 2: Non-tBRCA LOH Unknown181169 – 224
Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) Secondary · Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.

GroupValue95% CI
Part 2: tBRCA223188 – 275
Part 2: Non-tBRCA LOH+5754 – 112
Part 2: Non-tBRCA LOH-11363 – 165
Part 2: Non-tBRCA LOH Unknown11056 – 154
Overall Survival (Part 2 of Study) Secondary · All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.

Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.

GroupValue95% CI
Part 2: tBRCA22.716.7 – 28.6
Part 2: Non-tBRCA LOH+14.710.8 – 19.8
Part 2: Non-tBRCA LOH-13.39.1 – 16.0
Part 2: Non-tBRCA LOH Unknown14.17.4 – 20.1
Steady State Trough (Cmin) Level Rucaparib Concentrations Secondary · Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks

Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available.

Cycle 1 Day 15
GroupValue95% CI
Part 1 Overall2020.76± 1145.164
Part 2 Overall2276.37± 1587.586
Cycle 2 Day 1
GroupValue95% CI
Part 1 Overall1652.27± 935.503
Part 2 Overall1689.83± 1039.953
Cycle 3 Day 1
GroupValue95% CI
Part 1 Overall1557.32± 952.903
Part 2 Overall1552.09± 1054.346
Cycle 4 Day 1
GroupValue95% CI
Part 1 Overall1530.41± 765.940
Part 2 Overall1629.14± 1026.999

Adverse events — posted to ClinicalTrials.gov

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

Part 1 Overall
Serious: 54/204 (26%)
Deaths: 2/204
Part 2 Overall
Serious: 92/287 (32%)
Deaths: 18/287

Serious adverse events (101 terms)

ReactionSystemPart 1 OverallPart 2 Overall
AnaemiaBlood and lymphatic system disorders
Small intestinal obstructionGastrointestinal disorders
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
VomitingGastrointestinal disorders
NauseaGastrointestinal disorders
General physical health deteriorationGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Acute kidney injuryRenal and urinary disorders
DehydrationMetabolism and nutrition disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
ConstipationGastrointestinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
AscitesGastrointestinal disorders
Large intestinal obstructionGastrointestinal disorders
Obstruction gastricGastrointestinal disorders
SubileusGastrointestinal disorders
PainGeneral disorders
PneumoniaInfections and infestations
Other adverse events (62 terms — click to expand)

ReactionSystemPart 1 OverallPart 2 Overall
NauseaGastrointestinal disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
DysgeusiaNervous system disorders
Aspartate aminotransferase increasedInvestigations
Abdominal painGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
DiarrhoeaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
Blood creatinine increasedInvestigations
ThrombocytopeniaBlood and lymphatic system disorders
Weight decreasedInvestigations
DizzinessNervous system disorders
Abdominal distensionGastrointestinal disorders
Oedema peripheralGeneral disorders
Urinary tract infectionInfections and infestations
Platelet count decreasedInvestigations
HeadacheNervous system disorders
Abdominal pain upperGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
InsomniaPsychiatric disorders
Photosensitivity reactionSkin and subcutaneous tissue disorders
HypomagnesaemiaMetabolism and nutrition disorders
Upper respiratory tract infectionInfections and infestations
StomatitisGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Blood alkaline phosphatase increasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Neutrophil count decreasedInvestigations
DehydrationMetabolism and nutrition disorders
PruritisSkin and subcutaneous tissue disorders

Most-reported serious reactions: Anaemia, Small intestinal obstruction, Malignant neoplasm progression, Vomiting, Nausea, General physical health deterioration, Febrile neutropenia, Abdominal pain.

Data from ClinicalTrials.gov NCT01891344 adverse events section.

Sponsor's own description

The purpose of this study is to determine which patients with ovarian, fallopian tube, and primary peritoneal cancer will best respond to treatment with rucaparib.

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 in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial.
    Swisher EM, Lin KK, Oza AM, Scott CL, et al · · 2017 · cited 906× · PMID 27908594 · DOI 10.1016/s1470-2045(16)30559-9
  3. 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
  4. Secondary Somatic Mutations Restoring &lt;i&gt;RAD51C&lt;/i&gt; and &lt;i&gt;RAD51D&lt;/i&gt; Associated with Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma.
    Kondrashova O, Nguyen M, Shield-Artin K, Tinker AV, et al · · 2017 · cited 346× · PMID 28588062 · DOI 10.1158/2159-8290.cd-17-0419
  5. 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
  6. 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
  7. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma.
    Kondrashova O, Topp M, Nesic K, Lieschke E, et al · · 2018 · cited 241× · PMID 30266954 · DOI 10.1038/s41467-018-05564-z
  8. Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers.
    Watkins JA, Irshad S, Grigoriadis A, Tutt AN. · · 2014 · cited 232× · PMID 25093514 · DOI 10.1186/bcr3670

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