ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients

Sponsor
Clovis Oncology, Inc. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02855944
Collaborator
Foundation Medicine (Industry)
349
77
2
87
4.5
0.1

Study Details

Study Description

Brief Summary

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

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). The safety and efficacy of rucaparib has been evaluated in several Phase 1 and Phase 2 studies. An oral formulation is the focus of current development efforts. Rucaparib is currently being investigated as monotherapy in patients with cancer associated with breast cancer susceptibility gene 1 (BRCA1) or BRCA2 mutations.

While PARP inhibitors have demonstrated consistent robust clinical activity in patients with relapsed ovarian cancer associated with HRD, prospective studies evaluating efficacy and safety of PARPi versus standard of care chemotherapy have been limited. The primary purpose of this Phase 3 study is to compare the efficacy and safety of rucaparib versus chemotherapy as treatment for relapsed ovarian cancer in patients with a deleterious BRCA1/2 mutation in their tumor.

Study Design

Study Type:
Interventional
Actual Enrollment :
349 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Actual Study Start Date :
Mar 1, 2017
Actual Primary Completion Date :
Dec 3, 2020
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Rucaparib

Drug: Oral rucaparib 600 mg BID (twice a day) Other Names: CO-338 PF 01367338 AG 14699 Rubraca

Drug: Rucaparib
Tablets of rucaparib, at a dose of 600 mg, will be taken orally twice a day
Other Names:
  • CO-338
  • AG 14699
  • PF 01367338
  • Rubraca
  • Active Comparator: Chemotherapy

    Monotherapy platinum (cisplatin or carboplatin) or platinum-based doublet chemotherapy (carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision. Single agent paclitaxel will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.

    Drug: Chemotherapy
    Chemotherapy will be administered per local standard of care and regulations. Specific comparator will depend on platinum status and investigator decision.
    Other Names:
  • Cisplatin
  • carboplatin
  • carboplatin/paclitaxel
  • carboplatin/gemcitabine
  • paclitaxel
  • Outcome Measures

    Primary Outcome Measures

    1. Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population) [Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.

    2. Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population) [Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.

    Secondary Outcome Measures

    1. Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population) [Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.

    2. Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population) [Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.

    3. Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population) [Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    4. Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population) [Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    5. Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population) [Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

    6. Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population) [Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.]

      A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.

    7. Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population) [Baseline to the end of Cycle 6, or up to approximately 6 months]

      EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.

    8. Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population) [Baseline to the end of Cycle 6, or up to approximately 6 months]

      EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Be 18 years of age at the time the informed consent form is signed

    • Have a histologically confirmed diagnosis of high-grade serous or Grade 2 or Grade 3 endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer

    • Received ≥ 2 prior chemotherapy regimens and have relapsed or progressive disease as confirmed by radiologic assessment

    • Have biopsiable and evaluable disease. Note: biopsy is optional for patients known to harbor a BRCA1/2 mutation

    • Have sufficient archival formalin-fixed paraffin-embedded (FFPE) tumor tissue available for planned analyses

    Exclusion Criteria:
    • History of prior cancers except for those that have been curatively treated, with no evidence of cancer currently (provided all chemotherapy was completed >6 months prior and/or bone marrow transplant >2 years prior to first dose of rucaparib).

    • Prior treatment with any PARP inhibitor

    • Symptomatic and/or untreated central nervous system metastases

    • Pre-existing duodenal stent and/or any other gastrointestinal disorder or defect that would, in the opinion of the Investigator, interfere with absorption of rucaparib

    • Women who are pregnant or breast feeding

    • Hospitalization for bowel obstruction within 3 months prior to enrollment

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Rocky Mountain Cancer Center Denver Colorado United States 80218
    2 Augusta University Augusta Georgia United States 30912
    3 Hospital Haroldo Juacaba Instituto do Cancer do Ceara Fortaleza Ceara Brazil
    4 Instituto de Oncologia do Parana (IOP) Curitiba Parana Brazil
    5 União Brasileira de Educação e Assistência / Hospital São Lucas da PUCRS Porto Alegre RIO Grande DO SUL Brazil
    6 CEPON-Centro de pesquisas Oncologicas Florianópolis Santa Catarina Brazil
    7 Hospital do Cancer de Barretos Barretos SAO Paulo Brazil
    8 Instituto Nacional de Câncer Hospital do Câncer II Rio de Janeiro Brazil
    9 Hospital Pérola Byington - Centro de Referência da Saúde da Mulher Sao Paulo Brazil
    10 Hospital São Camilo Sao Paulo Brazil
    11 Tom Baker Cancer Center Calgary Alberta Canada
    12 The Ottawa Hospital - General Campus Ottawa Ontario Canada
    13 Princess Margaret Hospital Toronto Ontario Canada
    14 Centre Hospitalier de L'Universite de Montreal (CHUM) Montreal Quebec Canada
    15 CIUSSS de l'Estrie CHUS Sherbrooke Quebec Canada
    16 Masarykuv Onkologicky Ustav, Oddeleni komplexni klinicke onkologie Brno Jihormoravsky KRAJ Czechia
    17 Fakultni Nemocnice v Motole Praha 5 Praha Czechia
    18 Fakultní Nemocnice Ostrava Ostrava Czechia
    19 Všeobecná Fakultní Nemocnice v Praze Praha Czechia
    20 Debreceni Egyetem Klinikai Központ Debrecen Hajdu-bihar Hungary
    21 Országos Onkológiai Intézet Budapest Hungary
    22 Carmel Medical Center Haifa Israel
    23 Edith Wolfson Medical Center Holon Israel
    24 Hadassah Medical Organization Jerusalem Israel
    25 Rabin Medical Center Petach-Tikva Israel
    26 Chaim Sheba Medical Center Ramat Gan Israel
    27 Tel Aviv Sourasky Medical Center, Oncology Dept. Tel Aviv Israel
    28 Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi Bologna Italy
    29 Istituto per la Ricerca e la Cura del Cancro Istituto di Candiolo Candiolo Italy
    30 AO per l'emergenza Cannizzaro Catania Italy
    31 Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy
    32 Istituto Europeo di Oncologia Milano Italy
    33 Azienda Ospedaliero-Universitaria Policlinico di Modena Modena Italy
    34 Istituto Nazionale per lo studio e la cura dei tumori "Fondazione Pascale" Oncologia Medica Napoli Italy
    35 Fondazione Policlinico Universitario Agostino Gemelli Roma Italy
    36 Niepubliczny Zaklad Opieki Zdrowotnej Innowacyjna Medycyna Sp z o.o. Grzybnica West Pomeranian Voivodeship Poland
    37 Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie Bialystok Poland
    38 Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie Lublin Poland
    39 Wojewodzki Szpital Specjalistyczny w Olsztynie Olsztyn Poland
    40 Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Pozna Poznan Poland
    41 Pomorska Akademia Medyczna w Szczecinie, Samodzielny Publiczny Szpital Kliniczny Nr 2 Szczecin Poland
    42 Arkhangelsk Clinical Oncological Dispensary Arkhangelsk Russian Federation
    43 Kursk Regional Oncologic Dispensary Kursk Russian Federation
    44 Moscow Clinical Scientific and Practical Center of Moscow Healthcare Department Moscow Russian Federation 115478
    45 Omsk Region Clinical Oncologic Dispensary Omsk Russian Federation
    46 Pyatigorsk Oncological Dispensary Pyatigorsk Russian Federation
    47 Ryazan Regional Clinical Oncology Dispensary Ryazan Russian Federation
    48 Pavlov First Saint-Petersburg State Medical University Saint Petersburg Russian Federation
    49 State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region Saint Petersburg Russian Federation
    50 Saint Petersburg City Oncological Dispensary Saint-Petersburg Russian Federation
    51 Republican oncological dispensary of Republic of Mordovia Saransk Russian Federation
    52 State Healthcare Institution Oncologic Dispensary No. 2 - Health Department of Krasnodar Region Sochi Russian Federation
    53 Republic Clinical Oncology Dispensary of the Ministry of Healthcare of Republic of Bashkortostan Ufa Russian Federation
    54 Hospital Duran i Reynals Barcelona Spain
    55 Hospital Universitari Vall DHebron Barcelona Spain
    56 Hospital Universitari de Girona Doctor Josep Trueta Girona Spain
    57 Centro Oncologico Regional de Galicia La Coruna Spain
    58 Hospital Clinico San Carlos Madrid Spain
    59 Hospital Universitario Ramón y Cajal Madrid Spain
    60 MD Anderson Cancer Center Madrid Spain
    61 Universidad Autonoma de Madrid (UAM) - Hospital Universitario La Paz Madrid Spain
    62 Dnipropetrovsk City Multifield Clinical Hospital Number 4 Dnipropetrovsk Ukraine
    63 National Cancer Institute of the Ministry of Health of Ukraine Kyiv Ukraine
    64 Volyn Regional Oncology Dispensary Lutsk Ukraine
    65 Lviv Regional Oncology Dispensary Lviv Ukraine
    66 Sumy Regional Oncology Center Sumy Ukraine
    67 Zakarpattya Regional Clinical Oncological Dispensary Uzhgorod Ukraine
    68 The Christie NHS Foundation Trust - Clinical Trial Pharmacy Manchester England United Kingdom
    69 The Royal Marsden NHS Foundation Trust Sutton Surrey United Kingdom
    70 Cambridge University Hospitals NHS Foundation Trust Cambridge United Kingdom
    71 Velindre NHS Trust Cardiff United Kingdom
    72 University Hospital of Coventry and Warwickshire NHS Trust Coventry United Kingdom
    73 Derby Teaching Hospital NHS Foundation Trust Derby United Kingdom
    74 NHS Greater Glasgow and Clyde Glasgow United Kingdom
    75 University College London Hospitals London United Kingdom
    76 East and North Hertfordshire NHS Trust Middlesex United Kingdom
    77 Newcastle Hospitals NHS Foundation Trust Newcastle upon Tyne United Kingdom

    Sponsors and Collaborators

    • Clovis Oncology, Inc.
    • Foundation Medicine

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Clovis Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02855944
    Other Study ID Numbers:
    • CO-338-043
    First Posted:
    Aug 4, 2016
    Last Update Posted:
    Mar 3, 2022
    Last Verified:
    Feb 1, 2022

    Study Results

    Participant Flow

    Recruitment Details A total of 349 patients from 64 sites across 12 countries were enrolled in the initial Treatment Part of the study and randomized to receive rucaparib or chemotherapy. Patients randomized to chemotherapy had the option to cross over to receive rucaparib in the Crossover Part of the study upon progression of disease.
    Pre-assignment Detail
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm received oral rucaparib 600 mg twice a day (BID) in continuous 28-day cycles. Patients randomized to the chemotherapy arm received either weekly intravenous (IV) paclitaxel or IV platinum-based chemotherapy per investigator choice and per standard of care. The starting dose of weekly paclitaxel was 60 to 80 mg/m2 administered via IV infusion (ie, on Days 1, 8, and 15) in each 28-day cycle (with a week break from dosing on Day 22 in each cycle). The dosage and administration of single-agent cisplatin or carboplatin or doublet carboplatin/paclitaxel, carboplatin/gemcitabine, or cisplatin/gemcitabine IV infusion followed institutional guidelines for each agent. Upon progression of disease, patients had the option to cross over to rucaparib and receive oral rucaparib 600 mg BID in continuous 28-day cycles.
    Period Title: Period 1: Treatment
    STARTED 233 116
    COMPLETED 188 108
    NOT COMPLETED 45 8
    Period Title: Period 1: Treatment
    STARTED 0 74
    COMPLETED 0 47
    NOT COMPLETED 0 27

    Baseline Characteristics

    Arm/Group Title Rucaparib Chemotherapy Total
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm. Total of all reporting groups
    Overall Participants 233 116 349
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    58.0
    58.5
    58.0
    Sex: Female, Male (Count of Participants)
    Female
    233
    100%
    116
    100%
    349
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    0.4%
    0
    0%
    1
    0.3%
    Asian
    3
    1.3%
    0
    0%
    3
    0.9%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    4
    1.7%
    2
    1.7%
    6
    1.7%
    White
    219
    94%
    113
    97.4%
    332
    95.1%
    More than one race
    1
    0.4%
    0
    0%
    1
    0.3%
    Unknown or Not Reported
    5
    2.1%
    1
    0.9%
    6
    1.7%
    ECOG at Baseline (Count of Participants)
    ECOG 0
    125
    53.6%
    72
    62.1%
    197
    56.4%
    ECOG 1
    108
    46.4%
    44
    37.9%
    152
    43.6%
    Number of Prior Chemotherapy Regimens (Count of Participants)
    2
    134
    57.5%
    68
    58.6%
    202
    57.9%
    3
    58
    24.9%
    28
    24.1%
    86
    24.6%
    4
    23
    9.9%
    11
    9.5%
    34
    9.7%
    5
    7
    3%
    5
    4.3%
    12
    3.4%
    >5
    11
    4.7%
    4
    3.4%
    15
    4.3%
    Number of Prior Platinum Regimens (Count of Participants)
    1
    12
    5.2%
    6
    5.2%
    18
    5.2%
    2
    156
    67%
    74
    63.8%
    230
    65.9%
    3
    48
    20.6%
    28
    24.1%
    76
    21.8%
    4
    11
    4.7%
    7
    6%
    18
    5.2%
    5
    2
    0.9%
    1
    0.9%
    3
    0.9%
    >5
    4
    1.7%
    0
    0%
    4
    1.1%
    Randomization Stratification: Platinum Status (Count of Participants)
    Platinum resistant
    120
    51.5%
    59
    50.9%
    179
    51.3%
    Partially platinum-sensitive
    65
    27.9%
    31
    26.7%
    96
    27.5%
    Platinum sensitive
    48
    20.6%
    26
    22.4%
    74
    21.2%
    Combined Local and Central Lab BRCA Mutation Results (Count of Participants)
    BRCA1
    181
    77.7%
    79
    68.1%
    260
    74.5%
    BRCA2
    52
    22.3%
    36
    31%
    88
    25.2%
    Non-BRCA
    0
    0%
    1
    0.9%
    1
    0.3%
    Mutation Type (Count of Participants)
    Germline
    198
    85%
    95
    81.9%
    293
    84%
    Somatic
    35
    15%
    19
    16.4%
    54
    15.5%
    Not Available
    0
    0%
    2
    1.7%
    2
    0.6%
    Patients with a BRCA Reversion Mutation (Count of Participants)
    Count of Participants [Participants]
    13
    5.6%
    10
    8.6%
    23
    6.6%

    Outcome Measures

    1. Primary Outcome
    Title Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)
    Description The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Efficacy Population - All randomized patients in the treatment part of study with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation. As noted in the Baseline Characteristics Module, 1 patient in the Chemotherapy Arm did not have a BRCA mutation (Non-BRCA) and is therefore excluded from the overall number of patients analyzed.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 220 105
    Median (95% Confidence Interval) [Months]
    7.4
    5.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rucaparib, Chemotherapy
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0010
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.639
    Confidence Interval (2-Sided) 95%
    0.489 to 0.835
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)
    Description The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria 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 measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) Population - All randomized patients in the treatment part of study.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 233 116
    Median (95% Confidence Interval) [Months]
    7.4
    5.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rucaparib, Chemotherapy
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0017
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.665
    Confidence Interval (2-Sided) 95%
    0.516 to 0.858
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)
    Description A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.
    Time Frame Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Efficacy population with measurable disease at baseline. Efficacy population defined as all randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 211 96
    Number (95% Confidence Interval) [percentage of participants]
    40.3
    17.3%
    32.3
    27.8%
    4. Secondary Outcome
    Title Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)
    Description A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. 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. 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.
    Time Frame Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population with measurable disease at baseline. ITT population defined as all randomized patients.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 224 106
    Number (95% Confidence Interval) [percentage of participants]
    37.9
    16.3%
    30.2
    26%
    5. Secondary Outcome
    Title Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)
    Description A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Efficacy population with measurable disease at baseline and a confirmed response. Efficacy population defined as all randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation. As noted in the Baseline Characteristics Module, 1 patient in the Chemotherapy Arm did not have a BRCA mutation (Non-BRCA) and is therefore excluded from the overall number of patients analyzed.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 85 31
    Median (95% Confidence Interval) [months]
    9.4
    7.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rucaparib, Chemotherapy
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0401
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.589
    Confidence Interval (2-Sided) 95%
    0.356 to 0.976
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)
    Description A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
    Time Frame Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population with measurable disease at baseline and a confirmed response. ITT population defined as all randomized patients.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 85 32
    Median (95% Confidence Interval) [months]
    9.4
    7.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Rucaparib, Chemotherapy
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0240
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Cox Proportional Hazard
    Estimated Value 0.564
    Confidence Interval (2-Sided) 95%
    0.343 to 0.927
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)
    Description A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.
    Time Frame Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Efficacy population with measurable disease at baseline and/or CA-125 response evaluable. Efficacy population defined as all randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 217 101
    Number (95% Confidence Interval) [percentage of patients]
    50.7
    43.6
    8. Secondary Outcome
    Title Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)
    Description A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or 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. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response.
    Time Frame Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population with measurable disease at baseline and/or CA-125 response evaluable. ITT population defined as all randomized patients.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 230 111
    Number (95% Confidence Interval) [percentage of patients]
    47.8
    40.5
    9. Secondary Outcome
    Title Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population)
    Description EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.
    Time Frame Baseline to the end of Cycle 6, or up to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Efficacy population - All randomized patients with a deleterious BRCA mutation, excluding those identified to have a BRCA reversion mutation, and with a baseline value and at least one post-baseline value for the EORTC QLQ-C30 Global Health Status score during the first 6 cycles.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 197 91
    Least Squares Mean (Standard Error) [score on a scale]
    0.5
    (0.55)
    0.3
    (0.86)
    10. Secondary Outcome
    Title Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population)
    Description EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed.
    Time Frame Baseline to the end of Cycle 6, or up to approximately 6 months

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population - All randomized patients with a baseline value and at least one post-baseline value for the EORTC QLQ-C30 Global Health Status score during the first 6 cycles.
    Arm/Group Title Rucaparib Chemotherapy
    Arm/Group Description Patients randomized to the rucaparib arm. Patients randomized to the chemotherapy arm.
    Measure Participants 207 101
    Least Squares Mean (Standard Error) [score on a scale]
    0.6
    (0.54)
    0.4
    (0.82)

    Adverse Events

    Time Frame Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 3.5 years.
    Adverse Event Reporting Description Adverse events are reported for the Safety Population, defined as patients who received at least one dose of protocol-specified treatment.
    Arm/Group Title Rucaparib (Treatment Part) Chemotherapy (Treatment Part) Rucaparib (Crossover Part)
    Arm/Group Description Patients randomized to the rucaparib arm in the Treatment Part of the study. Patients randomized to the chemotherapy arm in the Treatment Part of the study. Patients randomized to chemotherapy who then crossed over upon disease progression and were treated with rucaparib.
    All Cause Mortality
    Rucaparib (Treatment Part) Chemotherapy (Treatment Part) Rucaparib (Crossover Part)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 15/232 (6.5%) 3/113 (2.7%) 2/74 (2.7%)
    Serious Adverse Events
    Rucaparib (Treatment Part) Chemotherapy (Treatment Part) Rucaparib (Crossover Part)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 62/232 (26.7%) 13/113 (11.5%) 17/74 (23%)
    Blood and lymphatic system disorders
    Anemia 19/232 (8.2%) 2/113 (1.8%) 4/74 (5.4%)
    Febrile neutropenia 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Leukopenia 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Neutropenia 4/232 (1.7%) 0/113 (0%) 0/74 (0%)
    Pancytopenia 0/232 (0%) 0/113 (0%) 1/74 (1.4%)
    Thrombocytopenia 5/232 (2.2%) 1/113 (0.9%) 0/74 (0%)
    Cardiac disorders
    Cardiac disorder 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Pericardial effusion 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Gastrointestinal disorders
    Abdominal distension 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Abdominal pain 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Ascites 2/232 (0.9%) 0/113 (0%) 0/74 (0%)
    Constipation 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Diarrhoea 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Dolichocolon acquired 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Gastrointestinal haemorrhage 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Haematemesis 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Ileus 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Intestinal obstruction 5/232 (2.2%) 0/113 (0%) 4/74 (5.4%)
    Large intestinal obstruction 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Large intestine perforation 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Megacolon 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Nausea 0/232 (0%) 0/113 (0%) 1/74 (1.4%)
    Pancreatitis 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Peritoneal adhesions 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Small intestine obstruction 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Subileus 1/232 (0.4%) 1/113 (0.9%) 0/74 (0%)
    Vomiting 3/232 (1.3%) 1/113 (0.9%) 0/74 (0%)
    General disorders
    Death 3/232 (1.3%) 0/113 (0%) 0/74 (0%)
    General physical health deterioration 2/232 (0.9%) 0/113 (0%) 0/74 (0%)
    Incarcerated hernia 0/232 (0%) 0/113 (0%) 1/74 (1.4%)
    Pyrexia 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Immune system disorders
    Drug hypersensitivity 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Infections and infestations
    Abdominal infection 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Cellulitis 0/232 (0%) 0/113 (0%) 1/74 (1.4%)
    Colonic abscess 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Cytomegalovirus colitis 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Device related infection 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Lower respiratory tract infection 1/232 (0.4%) 0/113 (0%) 1/74 (1.4%)
    Neutropenic sepsis 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Osteomyelitis 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Pneumonia 4/232 (1.7%) 0/113 (0%) 0/74 (0%)
    Sepsis 1/232 (0.4%) 0/113 (0%) 1/74 (1.4%)
    Septic shock 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Urinary tract infection 2/232 (0.9%) 1/113 (0.9%) 1/74 (1.4%)
    Injury, poisoning and procedural complications
    Femur fracture 0/232 (0%) 0/113 (0%) 1/74 (1.4%)
    Infusion related reaction 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Post procedural fever 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Radius fracture 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Seroma 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Tibia fracture 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Investigations
    Alanine aminotransferase increased 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Blood alkaline phosphatase increased 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Blood creatinine increased 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Platelet count decreased 2/232 (0.9%) 0/113 (0%) 0/74 (0%)
    Metabolism and nutrition disorders
    Cachexia 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Dehydration 2/232 (0.9%) 0/113 (0%) 0/74 (0%)
    Hypoalbuminaemia 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Hypomagnesaemia 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Hyponatraemia 1/232 (0.4%) 1/113 (0.9%) 0/74 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Intraductal proliferative breast lesion 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Malignant neoplasm progression 5/232 (2.2%) 2/113 (1.8%) 1/74 (1.4%)
    Myelodysplastic syndrome 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Nervous system disorders
    Cerebrovascular accident 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Depressed level of consciousness 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Ischaemic stroke 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Sciatica 0/232 (0%) 0/113 (0%) 1/74 (1.4%)
    Seizure 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Transient ischaemic attack 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Renal and urinary disorders
    Acute kidney injury 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Renal failure 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Reproductive system and breast disorders
    Fibrocystic breast disease 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/232 (0.4%) 0/113 (0%) 1/74 (1.4%)
    Pleural effusion 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Pneumonia aspiration 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Pulmonary embolism 1/232 (0.4%) 1/113 (0.9%) 0/74 (0%)
    Pulmonary oedema 1/232 (0.4%) 0/113 (0%) 0/74 (0%)
    Skin and subcutaneous tissue disorders
    Rash 0/232 (0%) 1/113 (0.9%) 0/74 (0%)
    Vascular disorders
    Deep vein thrombosis 3/232 (1.3%) 1/113 (0.9%) 1/74 (1.4%)
    Other (Not Including Serious) Adverse Events
    Rucaparib (Treatment Part) Chemotherapy (Treatment Part) Rucaparib (Crossover Part)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 220/232 (94.8%) 105/113 (92.9%) 63/74 (85.1%)
    Blood and lymphatic system disorders
    Anaemia 122/232 (52.6%) 35/113 (31%) 30/74 (40.5%)
    Leukopenia 20/232 (8.6%) 18/113 (15.9%) 5/74 (6.8%)
    Neutropenia 44/232 (19%) 28/113 (24.8%) 7/74 (9.5%)
    Thrombocytopenia 43/232 (18.5%) 13/113 (11.5%) 10/74 (13.5%)
    Lymphopenia 7/232 (3%) 7/113 (6.2%) 3/74 (4.1%)
    Cardiac disorders
    Sinus tachycardia 7/232 (3%) 6/113 (5.3%) 3/74 (4.1%)
    Gastrointestinal disorders
    Abdominal distension 13/232 (5.6%) 4/113 (3.5%) 4/74 (5.4%)
    Abdominal pain 54/232 (23.3%) 18/113 (15.9%) 13/74 (17.6%)
    Abdominal pain upper 20/232 (8.6%) 5/113 (4.4%) 8/74 (10.8%)
    Ascites 12/232 (5.2%) 2/113 (1.8%) 2/74 (2.7%)
    Constipation 36/232 (15.5%) 19/113 (16.8%) 14/74 (18.9%)
    Diarrhoea 46/232 (19.8%) 24/113 (21.2%) 12/74 (16.2%)
    Dyspepsia 19/232 (8.2%) 7/113 (6.2%) 2/74 (2.7%)
    Intestinal obstruction 5/232 (2.2%) 0/113 (0%) 4/74 (5.4%)
    Nausea 124/232 (53.4%) 36/113 (31.9%) 31/74 (41.9%)
    Stomatitis 11/232 (4.7%) 7/113 (6.2%) 3/74 (4.1%)
    Vomiting 79/232 (34.1%) 19/113 (16.8%) 17/74 (23%)
    Abdominal pain lower 12/232 (5.2%) 2/113 (1.8%) 3/74 (4.1%)
    General disorders
    Asthenia 64/232 (27.6%) 24/113 (21.2%) 12/74 (16.2%)
    Fatigue 55/232 (23.7%) 28/113 (24.8%) 15/74 (20.3%)
    Oedema peripheral 12/232 (5.2%) 8/113 (7.1%) 0/74 (0%)
    Pyrexia 22/232 (9.5%) 7/113 (6.2%) 2/74 (2.7%)
    Infections and infestations
    Upper respiratory tract infection 8/232 (3.4%) 3/113 (2.7%) 5/74 (6.8%)
    Urinary tract infection 15/232 (6.5%) 4/113 (3.5%) 4/74 (5.4%)
    Investigations
    Alanine aminotransferase increased 73/232 (31.5%) 12/113 (10.6%) 29/74 (39.2%)
    Aspartate aminotransferase increased 72/232 (31%) 8/113 (7.1%) 26/74 (35.1%)
    Blood alkaline phosphatase increased 15/232 (6.5%) 3/113 (2.7%) 9/74 (12.2%)
    Blood bilirubin increased 20/232 (8.6%) 0/113 (0%) 6/74 (8.1%)
    Blood cholesterol increased 6/232 (2.6%) 6/113 (5.3%) 6/74 (8.1%)
    Blood creatinine increased 32/232 (13.8%) 9/113 (8%) 15/74 (20.3%)
    Blood urea increased 9/232 (3.9%) 4/113 (3.5%) 5/74 (6.8%)
    Electrocardiogram QT prolonged 5/232 (2.2%) 6/113 (5.3%) 4/74 (5.4%)
    Electrocardiogram repolarisation abnormality 3/232 (1.3%) 4/113 (3.5%) 4/74 (5.4%)
    Neutrophil count decreased 5/232 (2.2%) 7/113 (6.2%) 2/74 (2.7%)
    Weight decreased 25/232 (10.8%) 3/113 (2.7%) 6/74 (8.1%)
    Metabolism and nutrition disorders
    Decreased appetite 44/232 (19%) 20/113 (17.7%) 19/74 (25.7%)
    Hypercholesterolaemia 9/232 (3.9%) 5/113 (4.4%) 5/74 (6.8%)
    Hyperglycaemia 16/232 (6.9%) 15/113 (13.3%) 4/74 (5.4%)
    Hypertriglyceridaemia 8/232 (3.4%) 7/113 (6.2%) 5/74 (6.8%)
    Hypomagnesaemia 14/232 (6%) 2/113 (1.8%) 2/74 (2.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 14/232 (6%) 9/113 (8%) 5/74 (6.8%)
    Back pain 12/232 (5.2%) 5/113 (4.4%) 9/74 (12.2%)
    Pain in extremity 8/232 (3.4%) 5/113 (4.4%) 4/74 (5.4%)
    Nervous system disorders
    Dizziness 12/232 (5.2%) 9/113 (8%) 2/74 (2.7%)
    Dysgeusia 39/232 (16.8%) 8/113 (7.1%) 10/74 (13.5%)
    Headache 17/232 (7.3%) 6/113 (5.3%) 2/74 (2.7%)
    Neuropathy peripheral 2/232 (0.9%) 16/113 (14.2%) 2/74 (2.7%)
    Neurotoxicity 1/232 (0.4%) 7/113 (6.2%) 2/74 (2.7%)
    Paraesthesia 4/232 (1.7%) 11/113 (9.7%) 1/74 (1.4%)
    Psychiatric disorders
    Insomnia 19/232 (8.2%) 7/113 (6.2%) 3/74 (4.1%)
    Respiratory, thoracic and mediastinal disorders
    Cough 19/232 (8.2%) 9/113 (8%) 7/74 (9.5%)
    Dyspnoea 25/232 (10.8%) 9/113 (8%) 6/74 (8.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 12/232 (5.2%) 38/113 (33.6%) 2/74 (2.7%)
    Photosensitivity reaction 10/232 (4.3%) 0/113 (0%) 5/74 (6.8%)
    Pruritus 9/232 (3.9%) 3/113 (2.7%) 7/74 (9.5%)
    Rash 12/232 (5.2%) 4/113 (3.5%) 4/74 (5.4%)
    Erythema 5/232 (2.2%) 2/113 (1.8%) 7/74 (9.5%)
    Vascular disorders
    Hypertension 8/232 (3.4%) 7/113 (6.2%) 4/74 (5.4%)

    Limitations/Caveats

    This study is ongoing. Results are presented for all data collected up to and including 30 September 2020, the visit cut-off date.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor's agreements with investigators require proposed public disclosures of trial results to be submitted to Sponsor for review prior to publication. Sponsor may request deletion of confidential information or a delay in publication to address intellectual property concerns, but Sponsor may not suppress publication of the trial results indefinitely. Sponsor may request delay of a single-center publication until after the release of a multi-site publication or an agreed upon period of time.

    Results Point of Contact

    Name/Title Medical Information Department
    Organization Clovis Oncology, Inc.
    Phone +1 415 409 7220
    Email medinfo@clovisoncology.com
    Responsible Party:
    Clovis Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02855944
    Other Study ID Numbers:
    • CO-338-043
    First Posted:
    Aug 4, 2016
    Last Update Posted:
    Mar 3, 2022
    Last Verified:
    Feb 1, 2022