ATLAS: Rucaparib in Patients With Locally Advanced or Metastatic Urothelial Carcinoma

• Sponsor: Clovis Oncology, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03397394
• Collaborator: Foundation Medicine (Industry)
• Enrollment: 97
• Locations: 64
• Arm: 1
• Actual Duration (Months): 19.5
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the ATLAS study is to determine how patients with locally advanced unresectable or metastatic urothelial carcinoma respond to treatment with rucaparib.

Condition or Disease	Intervention/Treatment	Phase
Bladder Cancer; Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Renal Pelvis Carcinoma; Ureter Carcinoma; Urinary Bladder Carcinoma; Urethra Carcinoma; Muscle Invasive Bladder Cancer	Drug: Rucaparib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 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 Locally Advanced or Metastatic Urothelial Carcinoma
• Actual Study Start Date: Jun 1, 2018
• Actual Primary Completion Date: Dec 12, 2019
• Actual Study Completion Date: Jan 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rucaparib Oral rucaparib (monotherapy)	Drug: Rucaparib; Rucaparib will be administered daily.; Other Names: CO-338

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) Per RECIST Version 1.1 [Time from first dose to date of progression, up to approximately 19 months]

   ORR is defined as the proportion of patients with a confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator. 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. Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator [Cycle 1 Day 1 to End of Treatment, up to approximately 10 months]

   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.

2. Overall Survival [The total study time for reporting of deaths was approximately 19 months.]

   Overall survival (OS) was defined as time from the date of first dose of rucaparib to the date of death due to any cause. Patients without a known date of death were to be censored on the date the patient was last known to be alive. A Kaplan-Meier analysis of OS was planned, however, due to early study termination and limited duration of OS follow-up, a descriptive summary of total deaths are presented. This includes deaths recorded on study (from first dose of study drug until 28 days after last dose of study drug), and deaths recorded in long-term follow-up (from last dose +28 days until death, loss to follow-up, withdrawal of consent, or study closure).

3. Pharmacokinetics - Trough (Cmin) Level Rucaparib Concentrations [From Cycle 2 Day 1 to Cycle 4 Day 1, or approximately 2 months]

   Plasma were collected for trough level PK analysis of rucaparib 1 hour before the morning dose on Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have histologically or cytologically confirmed locally advanced unresectable or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)

• Received 1 or 2 prior treatment regimens for advanced or metastatic disease

• Confirmed radiologic disease progression during or following recent treatment

• Mandatory biopsy is required during screening

• Measurable disease per RECIST v1.1

• Adequate organ function

• ECOG 0 or 1

Exclusion Criteria:

• Prior treatment with a PARP inhibitor

• Symptomatic and/or untreated CNS metastases

• Duodenal stent and/or any gastrointestinal disorder that may interfere with absorption of rucaparib

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pinnacle Oncology, Honor Health	Scottsdale	Arizona	United States	85258
2	University of California San Diego (UCSD), Moores Cancer Center	La Jolla	California	United States	92093
3	University of California, Los Angeles (UCLA)	Los Angeles	California	United States	90095
4	Universityof California, Irvine	Orange	California	United States	92868
5	Saint John's Health Center - John Wayne Cancer Institute (JWCI)	Santa Monica	California	United States	90404
6	Stanford University School of Medicine	Stanford	California	United States	94304
7	Hartford Health Care Cancer Institute	Hartford	Connecticut	United States	06102
8	Eastern Connecticut Hematology & Oncology Associates (ECHO)	Norwich	Connecticut	United States	06360
9	Medstar Georgetown University Medical Center	Washington	District of Columbia	United States	20007
10	Miami Cancer Institute, Baptist Health South Florida	Miami	Florida	United States	33176
11	Northwestern University, Chicago	Chicago	Illinois	United States	60611
12	Indiana University - Melvin and Bren Simon Cancer Center (IUSCC)	Indianapolis	Indiana	United States	46202
13	The University of Iowa and Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
14	Norton Cancer Center	Louisville	Kentucky	United States	40207
15	Ochsner Cancer Institute	New Orleans	Louisiana	United States	70121
16	University of Maryland, Marlene and Stewart Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
17	University of Michigan	Ann Arbor	Michigan	United States	48109
18	Minnesota Oncology Hematology P.A. (USO - US Oncology)	Minneapolis	Minnesota	United States	55404
19	Comprehensive Cancer Centers of Nevada (CCCN)	Las Vegas	Nevada	United States	89169
20	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
21	University of New Mexico UNM Cancer Research and Treatment Center	Albuquerque	New Mexico	United States	87102
22	New York Oncology Hematology, P.C. (USO - US Oncology)	Albany	New York	United States	12208
23	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
24	New York - Presbyterian Hospital-Weill Cornell Medical Center	New York	New York	United States	10021
25	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
26	Duke University, Duke Cancer Institute	Durham	North Carolina	United States	27710
27	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
28	Northwest Cancer Specialists P.C. (USO - US Oncology)	Portland	Oregon	United States	97062
29	Providence Portland Medical Center	Portland	Oregon	United States	97213
30	Oregon Health and Science University	Portland	Oregon	United States	97239
31	Lehigh Valley Health Network	Allentown	Pennsylvania	United States	18103
32	Penn State Hershey Medical Center	Hershey	Pennsylvania	United States	17033
33	Atlantic Urology Clinics	Myrtle Beach	South Carolina	United States	29572
34	University Oncology & Hematology	Chattanooga	Tennessee	United States	37403
35	Urology Associates	Nashville	Tennessee	United States	37209
36	Texas Oncology PA (USO - US Oncology)	Dallas	Texas	United States	76201
37	University of Texas, UT Health Science Center	Houston	Texas	United States	77030
38	University of Utah, Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
39	University of Virginia, Emily Couric Clinical Center	Charlottesville	Virginia	United States	22908
40	University of Washington / Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
41	Froedtert & Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
42	Centre de Lutte Contre le Cancer (CLCC) - Universite de Lyon - Centre Leon-Berard	Lyon		France	69008
43	Hopital Saint-Louis	Paris		France	75010
44	Centre de Lutte Contre le Cancer - Institut de Cancerologie de l'Ouest - Rene Gauducheau	Saint-Herblain		France	44805
45	Institut Universitaire du Cancer de Toulouse - Oncopole	Toulouse		France	31059
46	Institut Gustave Roussy	Villejuif		France	94805
47	Urologische und Kinderurologische Universitätsklinik im Malteser	Erlangen		Germany	91054
48	Universitatsklinikum Munster / Urologie und Kinderurologie	Münster		Germany	26133
49	Studienpraxis Urologie	Nurtingen		Germany	72622
50	Fondazionerca sul Cancro ONLUS - Istituto di Candiolo IRCCS	Candiolo		Italy	10060
51	IRCCS Ospedale San Raffaele - Medical Oncology Dept	Milano		Italy	20132
52	Fondazione IRCCS Istituto Nazionale Tumori	Milano		Italy	20133
53	Azienda Ospedaliera Universitaria Federico II Oncologia Medica	Naples		Italy	80131
54	Universidad de Navarra - Clinica Universitaria de Navarra	Pamplona	Navarre	Spain	31008
55	Hospital del Mar	Barcelona		Spain	08003
56	Hospital Santa Creu i Sant Pau	Barcelona		Spain	08025
57	Hospital Universitari Vall d'Hebron de Barcelona	Barcelona		Spain	08035
58	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
59	Clinica Universitaria de Navarra Madrid	Madrid		Spain	28027
60	MD Anderson Cancer Center	Madrid		Spain	28033
61	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
62	Hospital Clínico Universitario de Santiago de Compostela	Santiago De Compostela		Spain	15706
63	Sarah Cannon Research Institute - United Kingdom - London Office	London		United Kingdom	CH63 4JY
64	Guy's & St. Thomas' Hospital (London Oncology Clinic)	London		United Kingdom	W1G 6AF

Sponsors and Collaborators

• Clovis Oncology, Inc.
• Foundation Medicine

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 24, 2018
• Statistical Analysis Plan - Jan 31, 2018

More Information

Publications

None provided.

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT03397394
• Other Study ID Numbers: CO-338-085
• First Posted: Jan 12, 2018
• Last Update Posted: Oct 19, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Clovis Oncology, Inc.: PARP inhibitor; PARPi; HRD; ATLAS; homologous recombination; DNA repair; LOH; DNA defect; DNA anomaly; Rucaparib; MIBC
• Additional relevant MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Rucaparib

Study Results

Participant Flow

Recruitment Details	97 subjects were recruited from 40 sites across 6 countries.

Arm/Group Title	HRD Unknown	HRD Negative	HRD Positive
Arm/Group Description	Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.	Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH < 10% were considered HRD-negative.	Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.
Period Title: Overall Study
STARTED	47	30	20
COMPLETED	47	30	20
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	HRD Unknown	HRD Negative	HRD Positive	Total
Arm/Group Description	Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.	Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH < 10% were considered HRD-negative.	Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.	Total of all reporting groups
Overall Participants	47	30	20	97
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66.0	66.0	71.0	66.0
Sex: Female, Male (Count of Participants)
Female	9 19.1%	3 10%	9 45%	21 21.6%
Male	38 80.9%	27 90%	11 55%	76 78.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 14.9%	4 13.3%	1 5%	12 12.4%
Not Hispanic or Latino	29 61.7%	23 76.7%	17 85%	69 71.1%
Unknown or Not Reported	11 23.4%	3 10%	2 10%	16 16.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	2 4.3%	0 0%	0 0%	2 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	1 3.3%	0 0%	1 1%
Black or African American	1 2.1%	2 6.7%	0 0%	3 3.1%
White	32 68.1%	24 80%	18 90%	74 76.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	12 25.5%	3 10%	2 10%	17 17.5%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) Per RECIST Version 1.1
Description	ORR is defined as the proportion of patients with a confirmed response of complete response (CR) or partial response (PR) by RECIST v1.1 as assessed by the investigator. 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	Time from first dose to date of progression, up to approximately 19 months

Outcome Measure Data

Analysis Population Description

Intent-to-treat Population (ITT) with measurable disease at Baseline - The ITT population includes all patients who received at least 1 dose of rucaparib. One patient each in the HRD negative and HRD positive groups did not have measurable disease at Baseline.

Arm/Group Title	HRD Unknown	HRD Negative	HRD Positive	Overall
Arm/Group Description	Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.	Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH < 10% were considered HRD-negative.	Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.	All patients
Measure Participants	47	29	19	95
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Progression-free Survival (PFS) According to RECIST v1.1, as Assessed by the Investigator
Description	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.
Time Frame	Cycle 1 Day 1 to End of Treatment, up to approximately 10 months

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population - all patients who received at least 1 dose of rucaparib

Arm/Group Title	HRD Unknown	HRD Negative	HRD Positive	Overall
Arm/Group Description	Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.	Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH < 10% were considered HRD-negative.	Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.	All patients
Measure Participants	47	30	20	97
Median (95% Confidence Interval) [months]	1.8	1.8	1.4	1.8

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) was defined as time from the date of first dose of rucaparib to the date of death due to any cause. Patients without a known date of death were to be censored on the date the patient was last known to be alive. A Kaplan-Meier analysis of OS was planned, however, due to early study termination and limited duration of OS follow-up, a descriptive summary of total deaths are presented. This includes deaths recorded on study (from first dose of study drug until 28 days after last dose of study drug), and deaths recorded in long-term follow-up (from last dose +28 days until death, loss to follow-up, withdrawal of consent, or study closure).
Time Frame	The total study time for reporting of deaths was approximately 19 months.

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population - all patients who received at least 1 dose of rucaparib

Arm/Group Title	HRD Unknown	HRD Negative	HRD Positive	Overall
Arm/Group Description	Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.	Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH < 10% were considered HRD-negative.	Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.	All patients
Measure Participants	47	30	20	97
Count of Participants [Participants]	15 31.9%	15 50%	9 45%	39 40.2%

4. Secondary Outcome

Title	Pharmacokinetics - Trough (Cmin) Level Rucaparib Concentrations
Description	Plasma were collected for trough level PK analysis of rucaparib 1 hour before the morning dose on Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1.
Time Frame	From Cycle 2 Day 1 to Cycle 4 Day 1, or approximately 2 months

Outcome Measure Data

Analysis Population Description

Safety population - all patients who received at least 1 dose of rucaparib and who had at least 1 PK sample collected. The number analyzed at each timepoint includes only those participants who remained on study and with viable samples collected at that timepoint.

Arm/Group Title	HRD Unknown	HRD Negative	HRD Positive	Overall
Arm/Group Description	Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.	Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH < 10% were considered HRD-negative.	Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.	All patients
Measure Participants	24	13	10	47
Cycle 2 Day 1	2354.03 (2173.055)	1927.77 (1352.707)	1853.84 (1533.622)	2129.70 (1831.099)
Cycle 3 Day 1	2037.90 (1253.715)	1331.17 (357.010)	643.00 (688.722)	1647.33 (1068.270)
Cycle 4 Day 1	2225.00 (763.348)	2058.00 (705.280)	1585.00 (487.904)	2032.73 (672.891)

Adverse Events

Time Frame	Adverse events for each patient were reported from the first dose until 28 days after last dose of study drug, and the total study time for adverse event reporting was approximately 19 months.
Arm/Group Title	HRD Unknown		HRD Negative		HRD Positive		Overall
Arm/Group Description	Patients with HRD status unknown who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor genome-wide LOH was not tested or not determined were considered HRD unknown.		Patients with HRD status negative who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH < 10% were considered HRD-negative.		Patients with HRD status positive who received continuous dosing with rucaparib 600 mg twice a day (BID) in 28-day cycles. Patients whose tumor had genome-wide LOH ≥ 10% were considered HRD-positive.		All patients
All Cause Mortality
	HRD Unknown		HRD Negative		HRD Positive		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/47 (19.1%)		8/30 (26.7%)		7/20 (35%)		24/97 (24.7%)
Serious Adverse Events
	HRD Unknown		HRD Negative		HRD Positive		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/47 (42.6%)		14/30 (46.7%)		11/20 (55%)		45/97 (46.4%)
Blood and lymphatic system disorders
Anaemia	1/47 (2.1%)		1/30 (3.3%)		3/20 (15%)		5/97 (5.2%)
Pancytopenia	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Cardiac disorders
Cardiac arrest	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Myocardial infarction	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Gastrointestinal disorders
Constipation	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Gastric ulcer perforation	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Gastrointestinal haemorrhage	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Intestinal obstruction	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Small intestinal obstruction	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
General disorders
Disease progression	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
General physical health deterioration	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Pain	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Pyrexia	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Hepatobiliary disorders
Hepatocellular injury	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Infections and infestations
Lung infection	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Pneumonia	1/47 (2.1%)		1/30 (3.3%)		0/20 (0%)		2/97 (2.1%)
Pyelonephritis	2/47 (4.3%)		0/30 (0%)		0/20 (0%)		2/97 (2.1%)
Respiratory tract infection	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Sepsis	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Septic shock	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Urinary tract infection	1/47 (2.1%)		1/30 (3.3%)		0/20 (0%)		2/97 (2.1%)
Urosepsis	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Metabolism and nutrition disorders
Hyponatraemia	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Musculoskeletal and connective tissue disorders
Back pain	2/47 (4.3%)		0/30 (0%)		0/20 (0%)		2/97 (2.1%)
Pain in extremity	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Pubic pain	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	6/47 (12.8%)		9/30 (30%)		3/20 (15%)		18/97 (18.6%)
Nervous system disorders
Cerebrovascular accident	1/47 (2.1%)		1/30 (3.3%)		0/20 (0%)		2/97 (2.1%)
Psychiatric disorders
Confusional state	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Disorientation	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Mental status changes	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Renal and urinary disorders
Acute kidney injury	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Haematuria	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Hydronephrosis	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Urinary retention	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Hypoxia	1/47 (2.1%)		0/30 (0%)		0/20 (0%)		1/97 (1%)
Pleural effusion	0/47 (0%)		1/30 (3.3%)		0/20 (0%)		1/97 (1%)
Pulmonary embolism	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Respiratory failure	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Vascular disorders
Hypotension	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Other (Not Including Serious) Adverse Events
	HRD Unknown		HRD Negative		HRD Positive		Overall
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/47 (95.7%)		29/30 (96.7%)		19/20 (95%)		93/97 (95.9%)
Blood and lymphatic system disorders
Anaemia	16/47 (34%)		10/30 (33.3%)		8/20 (40%)		34/97 (35.1%)
Leukocytosis	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Neutropenia	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Thrombocytopenia	5/47 (10.6%)		6/30 (20%)		3/20 (15%)		14/97 (14.4%)
Gastrointestinal disorders
Abdominal pain	4/47 (8.5%)		5/30 (16.7%)		2/20 (10%)		11/97 (11.3%)
Abdominal pain upper	0/47 (0%)		1/30 (3.3%)		3/20 (15%)		4/97 (4.1%)
Anorectal discomfort	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Colitis	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Constipation	10/47 (21.3%)		5/30 (16.7%)		5/20 (25%)		20/97 (20.6%)
Diarrhoea	6/47 (12.8%)		5/30 (16.7%)		1/20 (5%)		12/97 (12.4%)
Dyspepsia	3/47 (6.4%)		1/30 (3.3%)		0/20 (0%)		4/97 (4.1%)
Dysphagia	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Flatulence	0/47 (0%)		2/30 (6.7%)		0/20 (0%)		2/97 (2.1%)
Nausea	26/47 (55.3%)		9/30 (30%)		6/20 (30%)		41/97 (42.3%)
Stomatitis	1/47 (2.1%)		0/30 (0%)		2/20 (10%)		3/97 (3.1%)
Swollen tongue	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Vomiting	13/47 (27.7%)		6/30 (20%)		3/20 (15%)		22/97 (22.7%)
General disorders
Asthenia	12/47 (25.5%)		4/30 (13.3%)		1/20 (5%)		17/97 (17.5%)
Chest pain	1/47 (2.1%)		2/30 (6.7%)		0/20 (0%)		3/97 (3.1%)
Chills	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Fatigue	21/47 (44.7%)		12/30 (40%)		7/20 (35%)		40/97 (41.2%)
Localized oedema	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Mucosal inflammation	1/47 (2.1%)		1/30 (3.3%)		2/20 (10%)		4/97 (4.1%)
Nodule	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Oedema peripheral	3/47 (6.4%)		1/30 (3.3%)		4/20 (20%)		8/97 (8.2%)
Pain	4/47 (8.5%)		3/30 (10%)		1/20 (5%)		7/97 (7.2%)
Peripheral swelling	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Pyrexia	4/47 (8.5%)		2/30 (6.7%)		3/20 (15%)		9/97 (9.3%)
Infections and infestations
Bacterial vaginosis	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Lung infection	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Sepsis	0/47 (0%)		1/30 (3.3%)		1/20 (5%)		2/97 (2.1%)
Sialoadenitis	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Urinary tract infection	4/47 (8.5%)		3/30 (10%)		3/20 (15%)		10/97 (10.3%)
Injury, poisoning and procedural complications
Back injury	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Fall	1/47 (2.1%)		0/30 (0%)		3/20 (15%)		4/97 (4.1%)
Head injury	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Joint injury	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Toxicity to various agents	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Investigations
Alanine aminotransferase increased	6/47 (12.8%)		2/30 (6.7%)		3/20 (15%)		11/97 (11.3%)
Aspartate aminotransferase increased	5/47 (10.6%)		5/30 (16.7%)		5/20 (25%)		15/97 (15.5%)
Blood alkaline phosphatase increased	3/47 (6.4%)		2/30 (6.7%)		0/20 (0%)		5/97 (5.2%)
Blood bilirubin increased	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Blood creatinine increased	6/47 (12.8%)		11/30 (36.7%)		4/20 (20%)		21/97 (21.6%)
Blood lactate dehydrogenase increased	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Lymphocyte count decreased	1/47 (2.1%)		0/30 (0%)		2/20 (10%)		3/97 (3.1%)
Neutrophil count decreased	1/47 (2.1%)		0/30 (0%)		2/20 (10%)		3/97 (3.1%)
Platelet count decreased	2/47 (4.3%)		3/30 (10%)		3/20 (15%)		8/97 (8.2%)
Transaminases increased	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Weight decreased	6/47 (12.8%)		7/30 (23.3%)		0/20 (0%)		13/97 (13.4%)
White blood cell count decreased	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Metabolism and nutrition disorders
Decreased appetite	14/47 (29.8%)		7/30 (23.3%)		7/20 (35%)		28/97 (28.9%)
Dehydration	5/47 (10.6%)		4/30 (13.3%)		1/20 (5%)		10/97 (10.3%)
Hyperglycaemia	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Hyperkalaemia	0/47 (0%)		1/30 (3.3%)		1/20 (5%)		2/97 (2.1%)
Hypoalbuminaemia	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Hypokalaemia	1/47 (2.1%)		1/30 (3.3%)		2/20 (10%)		4/97 (4.1%)
Hypomagnesaemia	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Hyponatraemia	2/47 (4.3%)		0/30 (0%)		2/20 (10%)		4/97 (4.1%)
Hypophosphataemia	6/47 (12.8%)		3/30 (10%)		1/20 (5%)		10/97 (10.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/47 (8.5%)		2/30 (6.7%)		1/20 (5%)		7/97 (7.2%)
Back pain	3/47 (6.4%)		3/30 (10%)		1/20 (5%)		7/97 (7.2%)
Flank pain	3/47 (6.4%)		2/30 (6.7%)		0/20 (0%)		5/97 (5.2%)
Groin pain	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Muscle twitching	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Muscular weakness	1/47 (2.1%)		0/30 (0%)		2/20 (10%)		3/97 (3.1%)
Musculoskeletal chest pain	0/47 (0%)		2/30 (6.7%)		0/20 (0%)		2/97 (2.1%)
Musculoskeletal pain	1/47 (2.1%)		2/30 (6.7%)		0/20 (0%)		3/97 (3.1%)
Neck pain	3/47 (6.4%)		0/30 (0%)		0/20 (0%)		3/97 (3.1%)
Pain in extremity	0/47 (0%)		2/30 (6.7%)		0/20 (0%)		2/97 (2.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Nervous system disorders
Dizziness	5/47 (10.6%)		0/30 (0%)		1/20 (5%)		6/97 (6.2%)
Dysgeusia	8/47 (17%)		7/30 (23.3%)		1/20 (5%)		16/97 (16.5%)
Paraesthesia	0/47 (0%)		1/30 (3.3%)		1/20 (5%)		2/97 (2.1%)
Peripheral sensory neuropathy	0/47 (0%)		1/30 (3.3%)		1/20 (5%)		2/97 (2.1%)
Somnolence	3/47 (6.4%)		0/30 (0%)		1/20 (5%)		4/97 (4.1%)
Psychiatric disorders
Insomnia	7/47 (14.9%)		2/30 (6.7%)		1/20 (5%)		10/97 (10.3%)
Renal and urinary disorders
Acute kidney injury	2/47 (4.3%)		0/30 (0%)		1/20 (5%)		3/97 (3.1%)
Haematuria	1/47 (2.1%)		4/30 (13.3%)		1/20 (5%)		6/97 (6.2%)
Reproductive system and breast disorders
Pelvic pain	1/47 (2.1%)		0/30 (0%)		1/20 (5%)		2/97 (2.1%)
Respiratory, thoracic and mediastinal disorders
Cough	0/47 (0%)		2/30 (6.7%)		1/20 (5%)		3/97 (3.1%)
Dyspnoea	5/47 (10.6%)		6/30 (20%)		1/20 (5%)		12/97 (12.4%)
Haemoptysis	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Oropharyngeal pain	0/47 (0%)		1/30 (3.3%)		1/20 (5%)		2/97 (2.1%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/47 (0%)		1/30 (3.3%)		1/20 (5%)		2/97 (2.1%)
Pruritus	1/47 (2.1%)		2/30 (6.7%)		1/20 (5%)		4/97 (4.1%)
Rash	2/47 (4.3%)		0/30 (0%)		1/20 (5%)		3/97 (3.1%)
Vascular disorders
Hypertension	3/47 (6.4%)		0/30 (0%)		0/20 (0%)		3/97 (3.1%)
Intermittent claudication	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)
Lymphoedema	0/47 (0%)		0/30 (0%)		1/20 (5%)		1/97 (1%)

Limitations/Caveats

The study was terminated early based on an interim analysis by the Data Monitoring Committee that demonstrated that ORR did not meet the protocol-defined continuance criteria. There were no confirmed responses observed.

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.