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

• Sponsor: Clovis Oncology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01891344
• Collaborator: Foundation Medicine (Industry), Myriad Genetics, Inc. (Industry)
• Enrollment: 491
• Locations: 75
• Arm: 1
• Actual Duration (Months): 94.9
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer; Epithelial Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer	Drug: Oral rucaparib	Phase 2

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.

Clinical data with PARP inhibitors indicate there is an ovarian cancer patient population beyond just those with germline BRCA (gBRCA) mutations that may benefit from treatment with a PARP inhibitor. This study will define a molecular signature of HRD in ovarian cancer that correlates with response to rucaparib and enables selection of appropriate ovarian cancer patients for treatment with rucaparib. The HRD signature will be based on an association between the extent of genomic scarring (a downstream consequence of HRD) in a patient's tumor and observed clinical benefit from rucaparib treatment. Genomic scarring can be assessed by quantifying the extent of loss of heterozygosity across the tumor genome (tumor genomic LOH). One of the main advantages of detecting tumor genomic LOH is that it can identify HRD tumors regardless of the underlying mechanisms, which include both known (i.e., BRCA mutations) and unknown genetic and other mechanisms.

Once determined, this signature will be prospectively applied to ARIEL2 PART 2 and ARIEL3. This Phase 2 study (ARIEL2) will also compare archival versus recently collected tumor tissue in order to validate the use of archival tumor tissue for assessment of HRD status in ARIEL3.

This study will include 2 parts:

PART 1 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received ≥1 prior platinum-based regimen and had platinum-sensitive disease

PART 2 (completed enrollment): Evaluation of HRD status and rucaparib efficacy in patients who received at least 3 prior chemotherapy regimens

Study Design

• Study Type: Interventional
• Actual Enrollment: 491 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label Study of Rucaparib in Patients With Platinum-Sensitive, Relapsed, High-Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (ARIEL2)
• Actual Study Start Date: Oct 30, 2013
• Actual Primary Completion Date: Nov 5, 2019
• Actual Study Completion Date: Sep 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ovarian cancer rucaparib	Drug: Oral rucaparib; 600 mg BID; Other Names: CO-338 PF 01367338 AG 14699

Outcome Measures

Primary Outcome Measures

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

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

2. Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) [Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.]

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

Secondary Outcome Measures

1. Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study) [Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.]

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

2. Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria [Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.]

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

3. Duration of Response Per RECIST v1.1 [Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.]

   Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.

4. Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study) [Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.]

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

5. Overall Survival (Part 2 of Study) [All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.]

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

6. Steady State Trough (Cmin) Level Rucaparib Concentrations [Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

The following eligibility criteria pertain to patients enrolling into PART 2 of the study:

Inclusion:

• 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 at least 3 prior chemotherapy regimens. Non-chemotherapy regimens and maintenance therapies administered as single agent treatment will not count as a chemotherapy regimen

• Relapsed/progressive disease as confirmed by CT scan

• Have biopsiable and measurable disease. Note: biopsy is optional for patients known to harbor a deleterious gBRCA mutation

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

Exclusion:

• 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

• Hospitalization for bowel obstruction within 3 months prior to enrollment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
2	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
3	Saint Jude Heritage Medical Center	Fullerton	California	United States	92835
4	University of California Los Angeles	Los Angeles	California	United States	90404
5	UC San Diego	San Diego	California	United States	92093
6	California Pacific Medical Center	San Francisco	California	United States	94115
7	University of California, San Francisco	San Francisco	California	United States	94158
8	Coastal Integrative Cancer Care	San Luis Obispo	California	United States	93401
9	Central Coast Medical Oncology	Santa Maria	California	United States	93454
10	Stanford University	Stanford	California	United States	94305
11	Rocky Mountain Cancer Centers	Lakewood	Colorado	United States	80228
12	Mayo Clinic Jacksonville	Jacksonville	Florida	United States	32224
13	Altus Research	Lake Worth	Florida	United States	33461
14	University of Miami Hospital & Clinics Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
15	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
16	UF Health Cancer Center	Orlando	Florida	United States	32806
17	Horizon BioAdvance	Lafayette	Indiana	United States	47905
18	Norton Cancer Institute	Louisville	Kentucky	United States	40241
19	Johns Hopkins Kimmel Cancer Center	Baltimore	Maryland	United States	21287
20	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
21	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
22	Mayo Clinic	Rochester	Minnesota	United States	55905
23	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
24	Comprehensive Cancer Centers of Nevada	Henderson	Nevada	United States	89014
25	Women's Cancer Care Associates	Albany	New York	United States	12208
26	New York University Langone Medical Center	New York	New York	United States	10016
27	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
28	Hope - A Woman's Cancer Institute	Asheville	North Carolina	United States	28006
29	University of Cincinnati Physicians Company	Cincinnati	Ohio	United States	45206
30	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
31	University of Oklahoma	Oklahoma City	Oklahoma	United States	73019
32	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
33	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
34	UPMC Cancer Center	Pittsburgh	Pennsylvania	United States	15213
35	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
36	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
37	Royal North Shore Hospital	Saint Leonards	New South Wales	Australia	2065
38	Prince of Wales Hospital	Sydney	New South Wales	Australia	2031
39	Royal Brisbane & Women's Hospital	Herston	Queensland	Australia	4029
40	Flinders Cancer Clinic - Flinders Medical Centre (FMC)	Bedford Park	South Australia	Australia	5042
41	Mercy Hospital for Women	Heidelberg	Victoria	Australia	3084
42	Royal Melbourne Hospital	Parkville	Victoria	Australia	3052
43	Crown Princess Mary Cancer Centre (Westmead Hospital)	Westmead	Wentworthville	Australia	NSW 2145
44	Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
45	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N4N2
46	Cross Cancer Centre	Edmonton	Alberta	Canada	T6G1Z2
47	British Columbia Cancer Agency	Kelowna	British Columbia	Canada	V1Y 5L3
48	BC Cancer Agency - Fraser Valley Centre	Surrey	British Columbia	Canada	V3V 1Z2
49	Vancouver Cancer Centre, British Columbia Cancer Agency (BCCA)	Vancouver	British Columbia	Canada	V5Z4E6
50	London Regional Cancer Centre	London	Ontario	Canada	N6A4L6
51	Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H8L6
52	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G2M9
53	Centre Hospitalier de L'Universite de Montreal	Montreal	Quebec	Canada	H2L 4M1
54	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
55	CHU de Québec - Université Laval	Québec		Canada	G1R 2J6
56	Institut Bergonie	Bordeaux	Aquitaine	France	33076
57	Hopital Tenon	Paris	Ile-de-France	France	75020
58	Hôpital Européen Georges-Pompidou	Paris	Ile-de-France	France	75908
59	Institut de cancerologie Gustave Roussy	Villejuif	Ile-de-France	France	94805
60	Institut Claudius Regaud	Toulouse	Midi-Pyrenees	France	31052
61	Centre Catherine de Sienne	Nantes	Pays De La Loire	France	44202
62	Centre Leon Berard	Lyon	Rhone-Alpes	France	69373
63	Centre Hospitalier Lyon Sud	Pierre-Benite	Rhone-Alpes	France	69495
64	Hospital Vall d'Hebron	Barcelona		Spain	8035
65	Instituto Valencia de Oncologia	Valencia		Spain	46009
66	Hospital Clinico Universitario de Valencia	Valencia		Spain	46010
67	Beatson West of Scotland Cancer Centre	Glasgow	Scotland	United Kingdom	G120YN
68	Royal Marsden Sutton Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
69	St James University Hospital	Leeds	West Yorkshire	United Kingdom	LS97TF
70	Addenbrooke's Hospital	Cambridge		United Kingdom	CB20QQ
71	Royal Marsden NHS Foundation Trust	London		United Kingdom	SW3 6JJ
72	Imperial College Healthcare NHS Trust - Hammersmith Hospital	London		United Kingdom	W120HS
73	University College London	London		United Kingdom	W1T4TJ
74	The Christie NHS Foundation Trust	Manchester		United Kingdom	M204BX
75	Sir Bobby Robson Cancer Trials Research Centre, Northern Centre for Cancer Care	Newcastle upon Tyne		United Kingdom	NE77DN

Sponsors and Collaborators

• Clovis Oncology, Inc.
• Foundation Medicine
• Myriad Genetics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 17, 2019
• Statistical Analysis Plan - May 16, 2019

More Information

Additional Information:

• ARIEL trials website

Publications

None provided.

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT01891344
• Other Study ID Numbers: CO-338-017
• First Posted: Jul 3, 2013
• Last Update Posted: Feb 4, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by Clovis Oncology, Inc.: ovarian cancer; fallopian tube cancer; primary peritoneal cancer; peritoneal cancer; platinum sensitive; relapsed disease; PARP Inhibitor; rucaparib; homologous recombination; homologous recombination deficiency; genomic scarring; loss of heterozygosity; CO-338; PF 01367338; AG 14699; platinum sensitive ovarian cancer; platinum sensitive fallopian tube cancer; platinum sensitive primary peritoneal cancer; platinum sensitive peritoneal cancer; gynecological cancer; Clovis; Clovis Oncology; ARIEL2; ARIEL 2; ARIEL3; ARIEL 3
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Peritoneal Neoplasms; Hypersensitivity; Rucaparib

Study Results

Participant Flow

Recruitment Details	491 subjects were recruited from 64 sites across 6 countries.

Arm/Group Title	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor. Part 1 enrolled patients who received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Patients without a BRCA mutation in their tumor, but have high LOH (loss of heterozygosity). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Patients without a BRCA mutation in their tumor, but have low LOH. Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 1 enrolled patients received ≥ 1 prior platinum-based regimen and had platinum-sensitive disease.	Patients with a deleterious BRCA mutation detected in their tumor. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Patients without a BRCA mutation in their tumor, but have high LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Patients without a BRCA mutation in their tumor, but have low LOH. Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s). Part 2 enrolled patients who received at least 3, but no more than 4, prior chemotherapy regimens.
Period Title: Overall Study
STARTED	40	82	70	12	84	73	107	23
COMPLETED	34	80	70	11	80	72	107	23
NOT COMPLETED	6	2	0	1	4	1	0	0

Baseline Characteristics

Arm/Group Title	tBRCA	Non-tBRCA LOH+	Non-tBRCA LOH-	Non-tBRCA LOH Unknown	Total
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Total of all reporting groups
Overall Participants	124	155	177	35	491
Age (years) [Median (Full Range) ]
Part 1	58.5	65	65	69.5	64.5
Part 2	60.5	61	64	62	63
Sex: Female, Male (Count of Participants)
Female	40 32.3%	82 52.9%	70 39.5%	12 34.3%	204 41.5%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Female	84 67.7%	73 47.1%	107 60.5%	23 65.7%	287 58.5%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.8%	0 0%	0 0%	0 0%	1 0.2%
Asian	3 2.4%	4 2.6%	5 2.8%	1 2.9%	13 2.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 0.8%	2 1.3%	1 0.6%	1 2.9%	5 1%
White	33 26.6%	67 43.2%	56 31.6%	10 28.6%	166 33.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 1.6%	9 5.8%	8 4.5%	0 0%	19 3.9%
American Indian or Alaska Native	1 0.8%	0 0%	0 0%	0 0%	1 0.2%
Asian	5 4%	4 2.6%	5 2.8%	0 0%	14 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 0.6%	0 0%	1 0.2%
Black or African American	0 0%	1 0.6%	0 0%	0 0%	1 0.2%
White	59 47.6%	46 29.7%	82 46.3%	18 51.4%	205 41.8%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	19 15.3%	22 14.2%	19 10.7%	5 14.3%	65 13.2%
Number of Prior Chemotherapy Regimens (Count of Participants)
0	0 0%	0 0%	0 0%	0 0%	0 0%
1	17 13.7%	45 29%	47 26.6%	10 28.6%	119 24.2%
2	14 11.3%	21 13.5%	16 9%	1 2.9%	52 10.6%
3	4 3.2%	13 8.4%	6 3.4%	1 2.9%	24 4.9%
4	4 3.2%	1 0.6%	0 0%	0 0%	5 1%
5	1 0.8%	1 0.6%	1 0.6%	0 0%	3 0.6%
>5	0 0%	1 0.6%	0 0%	0 0%	1 0.2%
0	0 0%	0 0%	0 0%	0 0%	0 0%
1	0 0%	0 0%	0 0%	0 0%	0 0%
2	0 0%	1 0.6%	1 0.6%	0 0%	2 0.4%
3	52 41.9%	44 28.4%	73 41.2%	17 48.6%	186 37.9%
4	32 25.8%	28 18.1%	31 17.5%	6 17.1%	97 19.8%
5	0 0%	0 0%	2 1.1%	0 0%	2 0.4%
>5	0 0%	0 0%	0 0%	0 0%	0 0%
Number of Prior Platinum Regimens (Count of Participants)
0	0 0%	0 0%	0 0%	0 0%	0 0%
1	17 13.7%	45 29%	47 26.6%	10 28.6%	119 24.2%
2	15 12.1%	25 16.1%	16 9%	1 2.9%	57 11.6%
3	6 4.8%	10 6.5%	6 3.4%	1 2.9%	23 4.7%
>3	2 1.6%	2 1.3%	1 0.6%	0 0%	5 1%
0	0 0%	0 0%	0 0%	0 0%	0 0%
1	2 1.6%	4 2.6%	7 4%	3 8.6%	16 3.3%
2	34 27.4%	31 20%	55 31.1%	7 20%	127 25.9%
3	40 32.3%	36 23.2%	44 24.9%	12 34.3%	132 26.9%
>3	8 6.5%	2 1.3%	1 0.6%	1 2.9%	12 2.4%
Platinum Sensitivity Status (Count of Participants)
Refractory	0 0%	0 0%	0 0%	0 0%	0 0%
Resistant	0 0%	1 0.6%	0 0%	1 2.9%	2 0.4%
Sensitive	40 32.3%	81 52.3%	70 39.5%	11 31.4%	202 41.1%
Refractory	12 9.7%	14 9%	18 10.2%	4 11.4%	48 9.8%
Resistant	41 33.1%	46 29.7%	56 31.6%	15 42.9%	158 32.2%
Sensitive	31 25%	13 8.4%	33 18.6%	4 11.4%	81 16.5%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD (Homologous Recombination Deficiency) Subgroups (Part 1 of Study)
Description	The primary efficacy endpoint of PFS is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST (Response Evaluation Criteria in Solid Tumors), as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Safety population by HRD subgroups: Consists of all Part 1 patients who received at least one dose of rucaparib.

Arm/Group Title	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Measure Participants	40	82	70	12
Median (95% Confidence Interval) [Days]	388	174	160	223

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: tBRCA, Part 1: Non-tBRCA LOH-
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.273
	Confidence Interval	(2-Sided) 95%; 0.170 to 0.437
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: Non-tBRCA LOH+, Part 1: Non-tBRCA LOH-
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.610
	Confidence Interval	(2-Sided) 95%; 0.428 to 0.871
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Objective Response Rate (ORR) by RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)
Description	The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed complete response (CR) or partial response (PR) on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Time Frame	Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

Arm/Group Title	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Measure Participants	84	73	107	23
Number (95% Confidence Interval) [percentage of participants]	31.0 25%	6.8 4.4%	5.6 3.2%	13.0 37.1%

3. Secondary Outcome

Title	Objective Response Rate (ORR) by RECIST v1.1 (Part 1 of Study)
Description	The confirmed response rate by RECIST v1.1 is defined as the percentage of patients with a confirmed CR or PR on subsequent tumor assessment at least 28 days after first response documentation. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
Time Frame	Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Safety population by HRD subgroups: Consist of all Part 1 patients who received at least one dose of rucaparib

Arm/Group Title	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Measure Participants	40	82	70	12
Number (95% Confidence Interval) [percentage of participants]	80.0 64.5%	28.0 18.1%	10.0 5.6%	33.3 95.1%

4. Secondary Outcome

Title	Objective Response Rate (ORR) by RECIST v1.1 and GCIG CA-125 Criteria
Description	The endpoint of ORR defined as the percentage of patients with a best response of CR or PR using RECIST v 1.1 or a response per Gynecologic Cancer InterGroup cancer antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. A response to CA-125 has occurred if there is at least a 50% decrease 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 withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Safety population by HRD subgroups: Consist of all Part 1 and Part 2 patients who received at least one dose of rucaparib.

Arm/Group Title	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Measure Participants	40	82	70	12	84	73	107	23
Number (95% Confidence Interval) [percentage of patients]	87.5	46.3	21.4	50.0	54.8	12.3	13.1	30.4

5. Secondary Outcome

Title	Duration of Response Per RECIST v1.1
Description	Duration of response (DOR) for any confirmed RECIST CR or PR measured from the date of the first occurrence of a response until the first occurrence of progressive disease (PD) per RECIST. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Any patients with an ongoing response were censored at the date of the last post-baseline scan. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least 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 withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Efficacy population by HRD subgroups. The overall number of patients analyzed includes only patients with confirmed RECIST CR or PR.

Arm/Group Title	Part 1: tBRCA	Part 1: Non-tBRCA LOH+	Part 1: Non-tBRCA LOH-	Part 1: Non-tBRCA LOH Unknown	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Measure Participants	32	23	7	4	26	5	6	3
Median (95% Confidence Interval) [Days]	281	329	169	225	176	282	314	181

6. Secondary Outcome

Title	Progression-free Survival (PFS) According to RECIST v1.1 in Molecularly-defined HRD Subgroups (Part 2 of Study)
Description	Progression-Free Survival (PFS) is calculated as 1+ the number of days from the first dose of study drug to disease progression by RECIST, as determined by the investigator or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measureable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Assessments every 8 weeks from C1D1 until disease progression, death or withdrawal of consent. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3 years.

Outcome Measure Data

Analysis Population Description

Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

Arm/Group Title	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Measure Participants	84	73	107	23
Median (95% Confidence Interval) [Days]	223	57	113	110

7. Secondary Outcome

Title	Overall Survival (Part 2 of Study)
Description	Overall survival (OS) is defined as the number of days from the date of first dose of study drug to the date of death (due to any cause). Patients without a known date of death will be censored on the date the patient was last known to be alive.
Time Frame	All patients in Part 2 were followed for survival, subsequent therapy, and secondary malignancy every 12 weeks until death, loss to follow-up, withdrawal of consent from study or study closure, whichever happened first, up to 7 years.

Outcome Measure Data

Analysis Population Description

Safety population by HRD subgroups: Consist of all Part 2 patients who received at least one dose of rucaparib.

Arm/Group Title	Part 2: tBRCA	Part 2: Non-tBRCA LOH+	Part 2: Non-tBRCA LOH-	Part 2: Non-tBRCA LOH Unknown
Arm/Group Description	Patients with a deleterious BRCA mutation detected in their tumor.	Patients without a BRCA mutation in their tumor, but have high LOH.	Patients without a BRCA mutation in their tumor, but have low LOH.	Patients without a BRCA mutation in their tumor, and have unknown LOH due to missing results and/or failed test result(s).
Measure Participants	84	73	107	23
Median (95% Confidence Interval) [Months]	22.7	14.7	13.3	14.1

8. Secondary Outcome

Title	Steady State Trough (Cmin) Level Rucaparib Concentrations
Description	Per protocol, the secondary PK endpoint, trough (Cmin) concentrations of rucaparib were summarized with descriptive statistics overall and by cycle in all patients with at least one PK sample collected. Blood samples for trough level PK analysis of rucaparib were drawn at the following timepoints only: on Day 15 of Cycle 1 and on Day 1 of Cycles 2, 3, and 4. Data for other timepoints is not available.
Time Frame	Cycle 1 Day 15 to Cycle 4 Day 1, or approximately 10 weeks

Outcome Measure Data

Analysis Population Description

All Part 1 and Part 2 patients with at least one PK sample collected

Arm/Group Title	Part 1 Overall	Part 2 Overall
Arm/Group Description	Includes all Part 1 patients	Includes all Part 2 patients
Measure Participants	196	267
Cycle 1 Day 15	2020.76 (1145.164)	2276.37 (1587.586)
Cycle 2 Day 1	1652.27 (935.503)	1689.83 (1039.953)
Cycle 3 Day 1	1557.32 (952.903)	1552.09 (1054.346)
Cycle 4 Day 1	1530.41 (765.940)	1629.14 (1026.999)

Adverse Events

Time Frame	Adverse events were reported from the time informed consent was obtained until 28 days after last dose of study drug, approximately 5 years.
Adverse Event Reporting Description	If a subject experiences the same preferred term (system organ class) multiple times, then the subject will be counted only once for that preferred term (system organ class). Adverse Events were monitored/assessed without regard to the subgroups.
Arm/Group Title	Part 1 Overall		Part 2 Overall
Arm/Group Description	All patients who participated in Part 1 who received at least one dose of rucaparib		All patients who participated in Part 2 who received at least one dose of rucaparib
All Cause Mortality
	Part 1 Overall		Part 2 Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/204 (1%)		18/287 (6.3%)
Serious Adverse Events
	Part 1 Overall		Part 2 Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/204 (26.5%)		92/287 (32.1%)
Blood and lymphatic system disorders
Anaemia	11/204 (5.4%)		12/287 (4.2%)
Febrile neutropenia	1/204 (0.5%)		6/287 (2.1%)
Granulocytosis	1/204 (0.5%)		0/287 (0%)
Leukocytosis	0/204 (0%)		1/287 (0.3%)
Neutropenia	1/204 (0.5%)		2/287 (0.7%)
Pancytopenia	0/204 (0%)		1/287 (0.3%)
Thrombocytopenia	2/204 (1%)		2/287 (0.7%)
Cardiac disorders
Acute coronary syndrome	0/204 (0%)		1/287 (0.3%)
Cardiac congestive failure	0/204 (0%)		1/287 (0.3%)
Myocardial infarction	1/204 (0.5%)		0/287 (0%)
Pericardial effusion	1/204 (0.5%)		0/287 (0%)
Congenital, familial and genetic disorders
Long QT syndrome congenital	1/204 (0.5%)		0/287 (0%)
Gastrointestinal disorders
Abdominal distension	0/204 (0%)		1/287 (0.3%)
Abdominal pain	1/204 (0.5%)		6/287 (2.1%)
Abdominal pain upper	0/204 (0%)		1/287 (0.3%)
Ascites	2/204 (1%)		1/287 (0.3%)
Colitis	0/204 (0%)		1/287 (0.3%)
Constipation	2/204 (1%)		3/287 (1%)
Diarrhoea	1/204 (0.5%)		1/287 (0.3%)
Ileus	1/204 (0.5%)		0/287 (0%)
Intestinal obstruction	1/204 (0.5%)		6/287 (2.1%)
Intestinal perforation	1/204 (0.5%)		0/287 (0%)
Large intestinal obstruction	1/204 (0.5%)		2/287 (0.7%)
Lower gastrointestinal haemorrhage	1/204 (0.5%)		0/287 (0%)
Nausea	3/204 (1.5%)		7/287 (2.4%)
Obstruction gastric	0/204 (0%)		2/287 (0.7%)
Rectal haemorrhage	1/204 (0.5%)		1/287 (0.3%)
Small intestinal obstruction	11/204 (5.4%)		8/287 (2.8%)
Subileus	0/204 (0%)		2/287 (0.7%)
Vomiting	1/204 (0.5%)		9/287 (3.1%)
General disorders
Asthenia	1/204 (0.5%)		4/287 (1.4%)
General physical health deterioration	0/204 (0%)		7/287 (2.4%)
Hyperthermia	0/204 (0%)		1/287 (0.3%)
Pain	0/204 (0%)		2/287 (0.7%)
Pyrexia	1/204 (0.5%)		4/287 (1.4%)
Hepatobiliary disorders
Bile duct obstruction	0/204 (0%)		1/287 (0.3%)
Hepatic failure	0/204 (0%)		1/287 (0.3%)
Hepatic haematoma	0/204 (0%)		1/287 (0.3%)
Infections and infestations
Appendicitis	0/204 (0%)		1/287 (0.3%)
Bacterial pyelonephritis	0/204 (0%)		1/287 (0.3%)
Bronchitis	1/204 (0.5%)		0/287 (0%)
Clostridium difficile colitis	1/204 (0.5%)		0/287 (0%)
Empyema	1/204 (0.5%)		0/287 (0%)
Gastroenteritis	1/204 (0.5%)		0/287 (0%)
Lower respiratory tract infection	1/204 (0.5%)		0/287 (0%)
Lung infection	0/204 (0%)		1/287 (0.3%)
Lymphangitis	1/204 (0.5%)		0/287 (0%)
Peritonitis	1/204 (0.5%)		0/287 (0%)
Pneumonia	2/204 (1%)		1/287 (0.3%)
Pyelonephritis	1/204 (0.5%)		2/287 (0.7%)
Sepsis	4/204 (2%)		1/287 (0.3%)
Septic shock	0/204 (0%)		1/287 (0.3%)
Staphylococcal infection	0/204 (0%)		1/287 (0.3%)
Urinary tract infection	3/204 (1.5%)		4/287 (1.4%)
Urosepsis	0/204 (0%)		1/287 (0.3%)
Injury, poisoning and procedural complications
Fall	1/204 (0.5%)		0/287 (0%)
Humerus fracture	1/204 (0.5%)		0/287 (0%)
Transfusion reaction	0/204 (0%)		1/287 (0.3%)
Investigations
Alanine aminotransferase increased	1/204 (0.5%)		0/287 (0%)
Blood cholesterol increased	1/204 (0.5%)		0/287 (0%)
Blood creatinine increased	1/204 (0.5%)		1/287 (0.3%)
Haemoglobin decreased	0/204 (0%)		1/287 (0.3%)
Lymphocyte count decreased	1/204 (0.5%)		0/287 (0%)
Neutrophil count decreased	1/204 (0.5%)		0/287 (0%)
Transaminases increased	1/204 (0.5%)		0/287 (0%)
Weight decreased	1/204 (0.5%)		0/287 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/204 (0%)		2/287 (0.7%)
Dehydration	1/204 (0.5%)		5/287 (1.7%)
Failure to thrive	0/204 (0%)		1/287 (0.3%)
Hypercalcaemia	0/204 (0%)		1/287 (0.3%)
Hypercholesterolaemia	1/204 (0.5%)		0/287 (0%)
Hyponatraemia	0/204 (0%)		2/287 (0.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/204 (0%)		1/287 (0.3%)
Back pain	0/204 (0%)		2/287 (0.7%)
Fracture pain	0/204 (0%)		1/287 (0.3%)
Pain in extremity	0/204 (0%)		1/287 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/204 (0%)		1/287 (0.3%)
Cancer pain	0/204 (0%)		2/287 (0.7%)
Malignant neoplasm progression	11/204 (5.4%)		10/287 (3.5%)
Metastatic neoplasm	0/204 (0%)		1/287 (0.3%)
Myelodysplastic syndrome	0/204 (0%)		1/287 (0.3%)
Neoplasm malignant	0/204 (0%)		1/287 (0.3%)
Nervous system disorders
Amnesia	1/204 (0.5%)		0/287 (0%)
Cerebrovascular accident	0/204 (0%)		1/287 (0.3%)
Syncope	1/204 (0.5%)		1/287 (0.3%)
Transient ischaemic attack	0/204 (0%)		2/287 (0.7%)
Psychiatric disorders
Mental status changes	1/204 (0.5%)		0/287 (0%)
Renal and urinary disorders
Acute kidney injury	6/204 (2.9%)		3/287 (1%)
Haematuria	0/204 (0%)		1/287 (0.3%)
Hydronephrosis	0/204 (0%)		2/287 (0.7%)
Reproductive system and breast disorders
Vaginal haemorrhage	0/204 (0%)		1/287 (0.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/204 (0.5%)		1/287 (0.3%)
Dyspnoea exertional	0/204 (0%)		1/287 (0.3%)
Haemothorax	0/204 (0%)		1/287 (0.3%)
Pleural effusion	2/204 (1%)		2/287 (0.7%)
Pleuritic pain	0/204 (0%)		1/287 (0.3%)
Pneumonia aspiration	0/204 (0%)		2/287 (0.7%)
Pulmonary embolism	1/204 (0.5%)		3/287 (1%)
Skin and subcutaneous tissue disorders
Dermatomyositis	0/204 (0%)		1/287 (0.3%)
Vascular disorders
Hypertension	0/204 (0%)		1/287 (0.3%)
Hypotension	0/204 (0%)		1/287 (0.3%)
Other (Not Including Serious) Adverse Events
	Part 1 Overall		Part 2 Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	203/204 (99.5%)		285/287 (99.3%)
Blood and lymphatic system disorders
Anaemia	72/204 (35.3%)		122/287 (42.5%)
Neutropenia	12/204 (5.9%)		18/287 (6.3%)
Thrombocytopenia	23/204 (11.3%)		44/287 (15.3%)
Gastrointestinal disorders
Abdominal distension	41/204 (20.1%)		31/287 (10.8%)
Abdominal pain	63/204 (30.9%)		89/287 (31%)
Abdominal pain lower	12/204 (5.9%)		12/287 (4.2%)
Abdominal pain upper	31/204 (15.2%)		35/287 (12.2%)
Ascites	12/204 (5.9%)		12/287 (4.2%)
Constipation	95/204 (46.6%)		81/287 (28.2%)
Diarrhoea	76/204 (37.3%)		83/287 (28.9%)
Dry mouth	11/204 (5.4%)		12/287 (4.2%)
Dyspepsia	24/204 (11.8%)		20/287 (7%)
Flatulence	13/204 (6.4%)		7/287 (2.4%)
Gastrooesophageal reflux disease	11/204 (5.4%)		15/287 (5.2%)
Nausea	161/204 (78.9%)		219/287 (76.3%)
Stomatitis	25/204 (12.3%)		15/287 (5.2%)
Vomiting	92/204 (45.1%)		125/287 (43.6%)
General disorders
Asthenia	24/204 (11.8%)		67/287 (23.3%)
Chills	16/204 (7.8%)		8/287 (2.8%)
Fatigue	140/204 (68.6%)		157/287 (54.7%)
Influenza like illness	11/204 (5.4%)		6/287 (2.1%)
Oedema peripheral	21/204 (10.3%)		38/287 (13.2%)
Pyrexia	29/204 (14.2%)		31/287 (10.8%)
Infections and infestations
Nasopharyngitis	15/204 (7.4%)		13/287 (4.5%)
Upper respiratory tract infection	27/204 (13.2%)		10/287 (3.5%)
Urinary tract infection	37/204 (18.1%)		33/287 (11.5%)
Investigations
Alanine aminotransferase increased	83/204 (40.7%)		85/287 (29.6%)
Aspartate aminotransferase increased	74/204 (36.3%)		92/287 (32.1%)
Blood alkaline phosphatase increased	19/204 (9.3%)		24/287 (8.4%)
Blood cholesterol increased	14/204 (6.9%)		13/287 (4.5%)
Blood creatinine increased	37/204 (18.1%)		65/287 (22.6%)
Neutrophil count decreased	20/204 (9.8%)		12/287 (4.2%)
Platelet count decreased	15/204 (7.4%)		36/287 (12.5%)
Weight decreased	42/204 (20.6%)		30/287 (10.5%)
White blood cell count decreased	13/204 (6.4%)		12/287 (4.2%)
Metabolism and nutrition disorders
Decreased appetite	85/204 (41.7%)		110/287 (38.3%)
Dehydration	16/204 (7.8%)		20/287 (7%)
Hypokalaemia	17/204 (8.3%)		19/287 (6.6%)
Hypomagnesaemia	13/204 (6.4%)		29/287 (10.1%)
Hyponatraemia	7/204 (3.4%)		15/287 (5.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	21/204 (10.3%)		19/287 (6.6%)
Back pain	33/204 (16.2%)		24/287 (8.4%)
Myalgia	17/204 (8.3%)		15/287 (5.2%)
Pain in extremity	21/204 (10.3%)		21/287 (7.3%)
Nervous system disorders
Dizziness	42/204 (20.6%)		35/287 (12.2%)
Dysgeusia	88/204 (43.1%)		93/287 (32.4%)
Headache	36/204 (17.6%)		35/287 (12.2%)
Lethargy	13/204 (6.4%)		5/287 (1.7%)
Neuropathy peripheral	11/204 (5.4%)		11/287 (3.8%)
Peripheral sensory neuropathy	11/204 (5.4%)		2/287 (0.7%)
Psychiatric disorders
Anxiety	14/204 (6.9%)		17/287 (5.9%)
Insomnia	23/204 (11.3%)		30/287 (10.5%)
Respiratory, thoracic and mediastinal disorders
Cough	35/204 (17.2%)		30/287 (10.5%)
Dyspnoea	46/204 (22.5%)		68/287 (23.7%)
Skin and subcutaneous tissue disorders
Alopecia	22/204 (10.8%)		7/287 (2.4%)
Dry skin	14/204 (6.9%)		6/287 (2.1%)
Erythema	7/204 (3.4%)		16/287 (5.6%)
Photosensitivity reaction	30/204 (14.7%)		18/287 (6.3%)
Pruritis	20/204 (9.8%)		16/287 (5.6%)
Rash	21/204 (10.3%)		13/287 (4.5%)
Vascular disorders
Hot flush	15/204 (7.4%)		10/287 (3.5%)
Hypertension	18/204 (8.8%)		12/287 (4.2%)

Limitations/Caveats

[Not Specified]

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.