ARIEL4: A Study of Rucaparib Versus Chemotherapy BRCA Mutant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 3 |
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
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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.- CO-338-043
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
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 |
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 |
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%
|
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%
|
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 |
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 |
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
|
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
|
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)
|
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
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 |
medinfo@clovisoncology.com |
- CO-338-043