Trial Outcomes & Findings for Radium Ra 223 With Enzalutamide Compared to Enzalutamide Alone in Men With Metastatic Castration Refractory Prostate Cancer (NCT NCT02199197)

NCT ID: NCT02199197

Last Updated: 2020-10-30

Results Overview

Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 49 participants
• Primary outcome timeframe: From prior to start of treatment to end of treatment or disease progression (approximately 6 months)
• Results posted on: 2020-10-30

Participant Flow

Participant milestones

Measure	Radium Ra 223 Dichloride and Enzalutamide Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kilobecquerel (kBq)/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Overall Study STARTED	35	14
Overall Study COMPLETED	35	12
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Two patients on the Enzalutamide only arm did not have subsequent N-Telopeptide labs drawn and were excluded from the N-Telopeptide analysis, so are excluded here as well.

Baseline characteristics by cohort

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=14 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Total n=49 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=35 Participants	5 Participants n=14 Participants	16 Participants n=49 Participants
Age, Categorical >=65 years	24 Participants n=35 Participants	9 Participants n=14 Participants	33 Participants n=49 Participants
Age, Continuous	69 years n=35 Participants	69.5 years n=14 Participants	69 years n=49 Participants
Sex: Female, Male Female	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Sex: Female, Male Male	35 Participants n=35 Participants	14 Participants n=14 Participants	49 Participants n=49 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=35 Participants	0 Participants n=14 Participants	1 Participants n=49 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=35 Participants	14 Participants n=14 Participants	48 Participants n=49 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Race (NIH/OMB) Asian	1 Participants n=35 Participants	0 Participants n=14 Participants	1 Participants n=49 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Race (NIH/OMB) Black or African American	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Race (NIH/OMB) White	34 Participants n=35 Participants	14 Participants n=14 Participants	48 Participants n=49 Participants
Race (NIH/OMB) More than one race	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=35 Participants	0 Participants n=14 Participants	0 Participants n=49 Participants
Serum N-Telopeptide Levels (Log2 scale)	3.42 nM BCE n=35 Participants • Two patients on the Enzalutamide only arm did not have subsequent N-Telopeptide labs drawn and were excluded from the N-Telopeptide analysis, so are excluded here as well.	3.41 nM BCE n=12 Participants • Two patients on the Enzalutamide only arm did not have subsequent N-Telopeptide labs drawn and were excluded from the N-Telopeptide analysis, so are excluded here as well.	3.42 nM BCE n=47 Participants • Two patients on the Enzalutamide only arm did not have subsequent N-Telopeptide labs drawn and were excluded from the N-Telopeptide analysis, so are excluded here as well.

PRIMARY outcome

Timeframe: From prior to start of treatment to end of treatment or disease progression (approximately 6 months)

Population: Per study protocol, only randomized patients with bone marker level measurements at baseline and Cycle 3 Day 1 will be evaluable for the primary efficacy outcome. 8 patients were assigned to Radium + Enzalutamide without randomization and were excluded from analysis. 2 patients on Enzalutamide alone did not reach Cycle 3 Day 1 and were excluded.

Patients had serum N-telopeptide labs drawn prior to the start of treatment and at the End of Treatment visit or at disease progression, whichever occurred first. The mean and standard deviation of the differences were calculated on a log 2 scale. Fold changes (post/pre) and 95% confidence intervals are reported.

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=27 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=12 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Fold Change in Serum N-telopeptides From Baseline	0.85 fold change Interval 0.76 to 0.94	1.34 fold change Interval 0.99 to 1.81

PRIMARY outcome

Timeframe: From first dose of study treatment to 30 days following last dose (approximately 7 months)

Adverse Events were assessed from start of Radium Ra 223 Dichloride or Enzalutamide treatment (whichever was started first) through 30 days after the last dose of either drug or until start of a new anti-cancer therapy, whichever came first. Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4.0. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. Reported below are the number of patients who experienced any grade 3-5 non-hematological AE. A full listing of AEs affecting 5% or more participants are listed in the Adverse Events module of the Results section.

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=14 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Number of Participants With Adverse Events	9 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 2 years (24 months)

Population: Two participants who dropped out prior to Cycle 3 were excluded from analysis

Prostate Specific Antigen (PSA) Progression Free Survival (PFS) is the time during with participants did not experience PSA progression. This is measured from the start of study therapy to the time of PSA progression. PSA progression is defined as a rise in PSA of at least 25% and at least 2 ng/ml from baseline or nadir. Kaplan-Meier methods were used.

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=12 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Prostate Specific Antigen (PSA) Progression Free Survival (PFS)	9.86 months Interval 4.67 to 22.5	3.34 months Interval 2.66 to Value is infinity because there were too few participants to get a real number.

SECONDARY outcome

Timeframe: Up to 2 years (24 months)

Population: Two participants who dropped out prior to Cycle 3 were excluded from analysis

Radiographic Progression Free Survival (PFS) is the time during with participants did not experience disease progression based on study imaging. This is measured from the start of study therapy to the time of radiographic progression. Radiographic progression was defined by the Prostate Cancer Working Group 2 (PCWG2) criteria, in which soft tissue disease is evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and bone lesions are evaluated separately under PCWG2 criteria. PCWG2 and RECIST 1.1 are established radiographic assessment protocols. Kaplan-Meier methods were used.

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=12 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Radiographic Progression Free Survival (PFS)	11.31 months Interval 9.07 to Value is infinity because there were too few participants to get a real number.	5.62 months Interval 2.76 to Value is infinity because there were too few participants to get a real number.

SECONDARY outcome

Timeframe: Up to 2 years (24 months)

Population: Two participants who dropped out prior to Cycle 3 were excluded from analysis

Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS) is the time during with participants did not experience Bone ALP progression. This is measured from the start of study therapy to the time of Bone ALP progression. Bone ALP progression defined as a rise in Bone ALP of at least 25% and at least 2 micrograms (mcg)/L from baseline or nadir. Kaplan-Meier methods were used.

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=12 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Bone Alkaline Phosphatase (ALP) Progression Free Survival (PFS)	NA months Too few participants demonstrated Bone ALP progression to obtain a median, and thus 95% confidence intervals are infinite.	4.64 months Interval 2.76 to Value is infinity because there were too few participants to get a real number.

SECONDARY outcome

Timeframe: Up to 2 years after start of study treatment

Population: Two participants who dropped out prior to Cycle 3 were excluded from analysis

Prostate Specific Antigen (PSA) Responses in participants were categorized based on decrease from baseline: less than 30% (<30%) decrease (including increases from baseline), greater than or equal to 30% (>=30%) decrease, greater than or equal to 50% (>=50%) decrease, and greater than or equal to 90% (>=90%) decrease. Count of participants in each category are provided

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=12 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Count of Prostate Specific Antigen (PSA) Responses <30%	6 Participants	6 Participants
Count of Prostate Specific Antigen (PSA) Responses >=30%	5 Participants	2 Participants
Count of Prostate Specific Antigen (PSA) Responses >=50%	9 Participants	2 Participants
Count of Prostate Specific Antigen (PSA) Responses >=90%	15 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 2 years after start of study treatment

Population: Two participants who dropped out prior to Cycle 3 were excluded from analysis

Radiographic Responses in participants were assessed using the Prostate Cancer Working Group 2 (PCWG2) criteria. Possible responses include Complete Response (CR) (complete disappearance of all metastatic disease on imaging), Partial Response (PR) (improvement in metastatic disease on imaging), Stable Disease (SD) (neither worsening nor improvement of metastatic disease on imaging), and Progressive Disease (PD) (worsening of metastatic disease on imaging). A count of participants in each category is provided here.

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=12 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Count of Radiographic Responses Complete Response (CR)	0 Participants	0 Participants
Count of Radiographic Responses Partial Response (PR)	3 Participants	0 Participants
Count of Radiographic Responses Stable Disease (SD)	28 Participants	8 Participants
Count of Radiographic Responses Progressive Disease (PD)	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to 40 months

Population: Two participants who dropped out prior to Cycle 3 were excluded from analysis

Overall Survival (OS) is the time during which participants did not pass away. This is measured from the start of study therapy to the time of death from any cause. Kaplan-Meier methods were used.

Outcome measures

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 Participants Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=12 Participants Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Overall Survival (OS)	26.0 months Interval 17.6 to Value is infinity because there were too few participants to get a real number.	21.0 months Interval 16.6 to Value is infinity because there were too few participants to get a real number.

Adverse Events

Radium Ra 223 Dichloride and Enzalutamide

Serious events: 7 serious events

Other events: 35 other events

Deaths: 15 deaths

Enzalutamide Alone

Serious events: 2 serious events

Other events: 12 other events

Deaths: 8 deaths

Serious adverse events

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 participants at risk Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=14 participants at risk Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Immune system disorders Anaphylaxis	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Back pain	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Gastrointestinal disorders - Other	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Infections and infestations Lung infection	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Neutrophil count decreased	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
General disorders Pain	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Nervous system disorders Syncope	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Infections and infestations Urinary tract infection	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.

Other adverse events

Measure	Radium Ra 223 Dichloride and Enzalutamide n=35 participants at risk Radium Ra 223 Dichloride and Enzalutamide administered concurrently for 6 28-day cycles. Radium Ra 223 Dichloride: Radium Ra 223 Dichloride, 55 kBq/kg body weight, administered as a bolus intravenous (IV) injection (up to 1 minute) on Day 1 of each cycle for 6 cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.	Enzalutamide Alone n=14 participants at risk Enzalutamide administered as a single agent for 6 28-day cycles. Enzalutamide: Enzalutamide 160 mg administered orally once a day (continuously) for 6 cycles.
Gastrointestinal disorders Abdominal pain	8.6% 3/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	14.3% 2/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Alkaline phosphatase increased	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	21.4% 3/14 • Number of events 4 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Blood and lymphatic system disorders Anemia	25.7% 9/35 • Number of events 13 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Metabolism and nutrition disorders Anorexia	34.3% 12/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Psychiatric disorders Anxiety	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 7/35 • Number of events 12 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	28.6% 4/14 • Number of events 5 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Back pain	20.0% 7/35 • Number of events 9 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Bloating	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Blood bilirubin increased	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Bone pain	14.3% 5/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	14.3% 2/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
General disorders Chills	5.7% 2/35 • Number of events 3 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Constipation	28.6% 10/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Respiratory, thoracic and mediastinal disorders Cough	17.1% 6/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Creatinine increased	2.9% 1/35 • Number of events 2 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • Number of events 2 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Psychiatric disorders Depression	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Diarrhea	54.3% 19/35 • Number of events 25 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Nervous system disorders Dizziness	11.4% 4/35 • Number of events 5 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Nervous system disorders Dysgeusia	14.3% 5/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.4% 4/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Ear and labyrinth disorders Ear and labyrinth disorders - Other	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
General disorders Edema limbs	17.1% 6/35 • Number of events 7 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
General disorders Facial pain	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
General disorders Fatigue	45.7% 16/35 • Number of events 20 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	21.4% 3/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Flatulence	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
General disorders Flu like symptoms	17.1% 6/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Gastroesophageal reflux disease	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Gastrointestinal disorders - Other	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	8.6% 3/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Infections and infestations Gum infection	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Reproductive system and breast disorders Gynecomastia	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Nervous system disorders Headache	14.3% 5/35 • Number of events 6 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Vascular disorders Hot flashes	11.4% 4/35 • Number of events 5 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Vascular disorders Hypertension	8.6% 3/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Metabolism and nutrition disorders Hypoalbuminemia	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Metabolism and nutrition disorders Hypocalcemia	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Metabolism and nutrition disorders Hypokalemia	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Metabolism and nutrition disorders Hyponatremia	11.4% 4/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Psychiatric disorders Insomnia	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Lymphocyte count decreased	51.4% 18/35 • Number of events 38 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	28.6% 4/14 • Number of events 6 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	14.3% 2/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Myalgia	22.9% 8/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	21.4% 3/14 • Number of events 6 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.6% 3/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	14.3% 2/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Nausea	45.7% 16/35 • Number of events 23 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Neck pain	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Neutrophil count decreased	40.0% 14/35 • Number of events 36 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
General disorders Non-cardiac chest pain	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Musculoskeletal and connective tissue disorders Pain in extremity	11.4% 4/35 • Number of events 8 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Cardiac disorders Palpitations	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Nervous system disorders Paresthesia	11.4% 4/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Nervous system disorders Peripheral sensory neuropathy	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Platelet count decreased	20.0% 7/35 • Number of events 9 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Respiratory, thoracic and mediastinal disorders Productive cough	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	14.3% 2/14 • Number of events 3 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Skin and subcutaneous tissue disorders Pruritus	14.3% 5/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Psychiatric disorders Psychiatric disorders - Other	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • Number of events 2 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Nervous system disorders Syncope	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Reproductive system and breast disorders Testicular pain	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Renal and urinary disorders Urinary frequency	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Renal and urinary disorders Urinary urgency	5.7% 2/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Ear and labyrinth disorders Vertigo	2.9% 1/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	7.1% 1/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Gastrointestinal disorders Vomiting	11.4% 4/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations Weight loss	11.4% 4/35 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Investigations White blood cell decreased	57.1% 20/35 • Number of events 47 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.	0.00% 0/14 • The collection of adverse events began after the first dose of study treatment and end 30 days after the last dose of study treatment (or until new cancer treatment was initiated, if sooner) (approximately 7 months). The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events also may have been detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.

Additional Information

Data Manager

Huntsman Cancer Institute Research Compliance Office

Phone: 801-585-0601

Email: compliance@hci.utah.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place