Trial Outcomes & Findings for Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer (NCT NCT02560051)

NCT ID: NCT02560051

Last Updated: 2018-11-28

Results Overview

Progression defined as increase in Prostate Specific Antigen (PSA) \>0.3 ng/mL over 2 measurements or larger/new lesion

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

19 participants

Primary outcome timeframe

From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months

Results posted on

2018-11-28

Participant Flow

Participant milestones

Participant milestones
Measure	Definitive Local Therapy 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Overall Study STARTED	6	8	5
Overall Study COMPLETED	3	4	4
Overall Study NOT COMPLETED	3	4	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hormone Therapy Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Total n=19 Participants Total of all reporting groups
Age, Continuous	66.5 years n=5 Participants	71 years n=7 Participants	60 years n=5 Participants	68 years n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	19 Participants n=4 Participants
Race/Ethnicity, Customized African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	5 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	6 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	19 Participants n=4 Participants
ECOG Performance Status 0	6 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	13 Participants n=4 Participants
ECOG Performance Status 1	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
ECOG Performance Status 2	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
ECOG Performance Status 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
ECOG Performance Status 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
ECOG Performance Status 5	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months

Progression defined as increase in Prostate Specific Antigen (PSA) \>0.3 ng/mL over 2 measurements or larger/new lesion

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by Number Who Progressed	0 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: about 10 months after treatment initiation

Population: Fewer were analyzed than the number that started or completed the study because not all participants were biopsied following treatment.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=1 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=3 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=4 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by Number of Participants With Pathology/Biopsy Positive for Disease	0 Participants	3 Participants	3 Participants

SECONDARY outcome

Timeframe: baseline

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by PSA Level	5.7 ng/mL Interval 0.1 to 27.7	15.8 ng/mL Interval 0.8 to 46.6	90.7 ng/mL Interval 17.5 to 2191.0

SECONDARY outcome

Timeframe: Cycle 1 Day 1, which is the day of treatment initiation

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by PSA Level	5.7 ng/mL Interval 0.01 to 27.7	9.7 ng/mL Interval 0.8 to 46.6	90.7 ng/mL Interval 17.5 to 90.7

SECONDARY outcome

Timeframe: Cycle 2 Day 1, which is about 8 weeks after treatment initiation

Population: Fewer were analyzed than the number that started study because not all participants completed the full number of cycles of treatment assigned. For some participants treatment was prematurely discontinued at different points through the course of treatment because of adverse events, progression, and participant withdrawal from study.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=7 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by PSA Level	0.01 ng/mL Interval 0.01 to 0.3	0.3 ng/mL Interval 0.1 to 0.6	3.8 ng/mL Interval 0.6 to 68.1

SECONDARY outcome

Timeframe: Cycle 3 Day 1, which is about 16 weeks after treatment initiation

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=5 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=6 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=4 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by PSA Level	0.01 ng/mL Interval 0.01 to 0.3	0.1 ng/mL Interval 0.1 to 0.8	0.9 ng/mL Interval 0.3 to 7.0

SECONDARY outcome

Timeframe: Cycle 4 Day 1, which is about 24 weeks after treatment initiation

Population: This time point is after 4 cycles of chemotherapy so no one in group "definitive local therapy" were analyzed. For the other groups fewer were analyzed than the number that started study because for some participants treatment was prematurely stopped at different points in treatment because of adverse events, progression, and withdrawal from study.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=5 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=4 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by PSA Level	—	0.01 ng/mL Interval 0.01 to 0.1	0.55 ng/mL Interval 0.2 to 4.1

SECONDARY outcome

Timeframe: Cycle 5 Day 1, which is about about 32 weeks after treatment initiation

Population: This time point is after 5 cycles of chemo so so no participants in the groups that had only 3/4 cycles were included. For the other group fewer were analyzed than the number that started study because for some treatment was prematurely stopped at different points in treatment because of adverse events, progression, and withdrawal from study.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=3 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by PSA Level	—	—	0.5 ng/mL Interval 0.1 to 2.6

SECONDARY outcome

Timeframe: end of treatment, which is about about 8 weeks after the start of the last cycle

Population: Fewer were analyzed than the number that started study because some participants were taken off study at different points in treatment or follow-up because of adverse events, progression, and withdrawal from study.

Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. The time point is the end of treatment, which is about about 8 weeks after the start of the last cycle. For the arm completing 3 cycles, the time point is 24 weeks after treatment initiation. For the arm completing 4 cycles, the time point is 32 weeks after treatment initiation. For the arm completing 5 cycles, the time point is 40 weeks after treatment initiation.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=7 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by PSA Level	0.01 ng/mL Interval 0.01 to 0.2	0.01 ng/mL Interval 0.01 to 0.2	1.4 ng/mL Interval 0.1 to 34.4

SECONDARY outcome

Timeframe: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months

PSA progression defined as increase in Prostate Specific Antigen (PSA) \>0.3 ng/mL over 2 measurements

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Efficacy as Measured by Number Who PSA Progressed	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: post cycle 1, which is about 8 weeks after treatment initiation

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Quality of Life Measure by FACT-P Scale	97 units on a scale Interval 62.0 to 135.0	99 units on a scale Interval 87.0 to 123.0	105 units on a scale Interval 58.0 to 115.0

SECONDARY outcome

Timeframe: post cycle 2, which is about 16 weeks after treatment initiation

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=5 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=6 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Quality of Life Measure by FACT-P Scale	94 units on a scale Interval 62.0 to 114.0	97 units on a scale Interval 85.0 to 124.0	102 units on a scale Interval 58.0 to 121.0

SECONDARY outcome

Timeframe: post cycle 3, which is about 24 weeks after treatment initiation

Population: Fewer were analyzed than the number that started study because some participants were taken off study at different points throughout the study because of adverse events, progression, and participant withdrawal from study. Additionally, some participants did not wish to complete the FACT-P questionnaire.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=1 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=5 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=4 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Quality of Life Measure by FACT-P Scale	79 units on a scale Interval 79.0 to 79.0	94 units on a scale Interval 89.0 to 123.0	114 units on a scale Interval 101.0 to 121.0

SECONDARY outcome

Timeframe: post cycle 4, which is about 32 weeks after treatment initiation

Population: This is after 4 cycles of chemo so no one in group "definitive local therapy" were analyzed. For the other groups fewer were analyzed than the number that started study because for some participants treatment or follow-up was prematurely stopped at different points because of adverse events, progression, and withdrawal from study.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=3 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=4 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Quality of Life Measure by FACT-P Scale	—	96 units on a scale Interval 93.0 to 126.0	113 units on a scale Interval 99.0 to 121.0

SECONDARY outcome

Timeframe: post cycle 5, which is about about 40 weeks after treatment initiation

Outcome measures

Outcome measures
Measure	Definitive Local Therapy 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=4 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Quality of Life Measure by FACT-P Scale	—	—	107 units on a scale Interval 89.0 to 117.0

SECONDARY outcome

Timeframe: about 12 weeks after completion of the last cycle

The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL. The time point is about 12 weeks after completion of the last cycle. For the arm completing 3 cycles, the time point is 36 weeks after treatment initiation. For the arm completing 4 cycles, the time point is 44 weeks after treatment initiation. For the arm completing 5 cycles, the time point is 52 weeks after treatment initiation.

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=3 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=4 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=2 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Quality of Life Measure by FACT-P Scale	94 units on a scale Interval 83.0 to 115.0	118 units on a scale Interval 92.0 to 142.0	99 units on a scale Interval 93.0 to 105.0

SECONDARY outcome

Timeframe: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months

Outcome measures

Outcome measures
Measure	Definitive Local Therapy n=6 Participants 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 Participants 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 Participants 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Safety of Drug Regimen as Measured by Number of Adverse Events	115 adverse event	270 adverse event	166 adverse event

Adverse Events

Definitive Local Therapy

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Nodal Only/Low-volume Bone

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

High Volume/no Prior tx

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Marka Lyons, Research Manager

The University of Texas Health Science Center at Houston

Phone: 713-500-6919

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Definitive Local Therapy n=6 participants at risk 3 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 12 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	Nodal Only/Low-volume Bone n=8 participants at risk 4 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 18 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days	High Volume/no Prior tx n=5 participants at risk 5 cycles of chemotherapy (doxorubicin, ketoconazole, docetaxel and estramustine) + 24 months ADT (degarelix) Doxorubicin: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive doxorubicin (20 mg/m2 as a 24-hour intravenous infusion on day 1 of each applicable week) Ketoconazole: In weeks 1, 3, and 5 of each 8-week cycle, participants will receive ketoconazole (400 mg orally 3 times daily for 7 days) Docetaxel: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive docetaxel (35 mg/m2 intravenously on day 1 of each applicable week) Estramustine: In weeks 2, 4, and 6 of each 8-week cycle, participants will receive estramustine (280 mg orally 3 times daily for 7 days) Degarelix: The starting dose (240 mg given as two injections of 120 mg each) is followed by maintenance doses of 80 mg administered as a single injection every 28 days
Blood and lymphatic system disorders Anemia	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 2 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Cardiac disorders Sinus Tachycardia	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 2 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Gastrointestinal disorders Abdominal Pain	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Gastrointestinal disorders Nausea	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Gastrointestinal disorders Vomiting	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
General disorders Fever	50.0% 3/6 • Number of events 3 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	25.0% 2/8 • Number of events 2 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
General disorders Chills	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
General disorders Fatigue	16.7% 1/6 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/8 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Infections and infestations Urinary Tract Infection	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Infections and infestations Sepsis	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Investigations Creatinine Increased	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Investigations White blood cell decreased	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	25.0% 2/8 • Number of events 3 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	25.0% 2/8 • Number of events 2 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Metabolism and nutrition disorders Anorexia	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	25.0% 2/8 • Number of events 2 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Respiratory, thoracic and mediastinal disorders Cough	16.7% 1/6 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Respiratory, thoracic and mediastinal disorders Post nasal drip	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	25.0% 2/8 • Number of events 2 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	12.5% 1/8 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders, Pulmonary inflammation	16.7% 1/6 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/8 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.
Vascular disorders Thromboembolic event	16.7% 1/6 • Number of events 1 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/8 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.	0.00% 0/5 • From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months.