Trial Outcomes & Findings for Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases (NCT NCT00081159)

Last Updated: 2016-11-10

Results Overview

Study's primary endpoint of PFS duration/time to progression was defined as the time from the date of randomization to the date of first evidence of disease progression or patient death. Prostate-specific antigen (PSA) progression is usually the first evidence of progression. PSA progression is defined as a 25% increase over the baseline or the nadir provided that the increase is a minimum of 1 ng/ml.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

Up to 90 months with evaulation in 4 week intervals for up to 6 months of treatment, then follow up until disease progression

Results posted on

2016-11-10

Participant Flow

Recruitment period: July 6, 2004 to July 5, 2007. Recruitment done in medical clinic settings.

One participant of 80 male participants withdrew consent after the screening procedures therefore was not randomized nor treated and is excluded from the trial.

Participant milestones

Participant milestones
Measure	HAT, Doxorubicin, Zoledronate + Strontium Chloride Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin intravenous (IV) on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.	HAT, Doxorubicin + Zoledronate Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses.
Overall Study STARTED	39	40
Overall Study COMPLETED	37	35
Overall Study NOT COMPLETED	2	5

Reasons for withdrawal

Reasons for withdrawal
Measure	HAT, Doxorubicin, Zoledronate + Strontium Chloride Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin intravenous (IV) on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.	HAT, Doxorubicin + Zoledronate Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses.
Overall Study Withdrawal by Subject	0	3
Overall Study Myelosuppression prior to treatment	0	1
Overall Study Lost to Follow-up	2	1

Baseline Characteristics

Hormone Ablation Therapy, Doxorubicin, and Zoledronate With or Without Strontium 89 in Treating Patients With Androgen-Dependent Prostate Cancer and Bone Metastases

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HAT, Doxorubicin, Zoledronate + Strontium Chloride n=39 Participants Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.	HAT, Doxorubicin + Zoledronate n=40 Participants Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses.	Total n=79 Participants Total of all reporting groups
Age, Continuous	62 years n=93 Participants	63 years n=4 Participants	63 years n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	39 Participants n=93 Participants	40 Participants n=4 Participants	79 Participants n=27 Participants
Race/Ethnicity, Customized White	37 participants n=93 Participants	34 participants n=4 Participants	71 participants n=27 Participants
Race/Ethnicity, Customized Black	2 participants n=93 Participants	3 participants n=4 Participants	5 participants n=27 Participants
Race/Ethnicity, Customized Not Reported	0 participants n=93 Participants	3 participants n=4 Participants	3 participants n=27 Participants
Region of Enrollment United States	39 participants n=93 Participants	40 participants n=4 Participants	79 participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 90 months with evaulation in 4 week intervals for up to 6 months of treatment, then follow up until disease progression

Population: Intent to treat population analysis.

Outcome measures

Outcome measures
Measure	HAT, Doxorubicin, Zoledronate + Strontium Chloride n=39 Participants Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.	HAT, Doxorubicin + Zoledronate n=40 Participants Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses.
Progression Free Survival (PFS)	12.9 Months Interval 8.9 to 72.5	18.5 Months Interval 9.7 to 49.4

SECONDARY outcome

Timeframe: Week 13

Population: Five participants in the non-Strontium arm were not evaluable for this outcome, four withdrew prior to treatment, and one had disease progression that precluded inclusion. Two participants in the Strontium arm were lost to follow up therefore excluded from analysis as well.

Bone scan performed at baseline and at Week 13 provided if baseline scan was positive for metastases. A major bone scan response was considered with a substantial resolution of participant bone metastases on the bone scans, i.e. complete resolution of the osseous metastases on the bone scan.

Outcome measures

Outcome measures
Measure	HAT, Doxorubicin, Zoledronate + Strontium Chloride n=37 Participants Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.	HAT, Doxorubicin + Zoledronate n=35 Participants Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses.
Major Bone Scan Response	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 90 months

Population: Intent to treat population analysis.

Overall Survival defined as the length of time from the start of treatment till time that participants are still alive.

Outcome measures

Outcome measures
Measure	HAT, Doxorubicin, Zoledronate + Strontium Chloride n=39 Participants Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.	HAT, Doxorubicin + Zoledronate n=40 Participants Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses.
Overall Survival (OS)	47.4 Months Interval 35.9 to 87.3	53.5 Months Interval 38.0 to Not attainable, time constraint

Adverse Events

HAT, Doxorubicin, Zoledronate + Strontium Chloride

Serious events: 0 serious events

Other events: 24 other events

Deaths: 0 deaths

HAT, Doxorubicin + Zoledronate

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Shi-Ming Tu, MD

University of Texas (UT) MD Anderson Cancer Center

Phone: 1-877-632-6789

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	HAT, Doxorubicin, Zoledronate + Strontium Chloride n=39 participants at risk Arm I: Hormonal ablative therapy (HAT) comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses; and a single dose of strontium chloride Sr 89 IV over 1-2 minutes on day 1.	HAT, Doxorubicin + Zoledronate n=37 participants at risk Arm II: HAT, doxorubicin, and zoledronate as in arm I. HAT comprising luteinizing hormone-releasing hormone agonist (e.g., leuprolide or goserelin) continuously during study treatment OR bilateral orchiectomy; doxorubicin IV on days 1, 8, and 15 every 28 days for 2 courses; zoledronate IV over 15 minutes on day 1 every 28 days for 6 courses.
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	5.4% 2/37 • Number of events 2 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Investigations Alanine aminotransferase increased (Alt, Sgpt)	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Metabolism and nutrition disorders Anorexia	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Investigations Aspartate aminotransferase increased (Ast, Sgot)	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Investigations Bilirubin Increased	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Gastrointestinal disorders Constipation	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Immune system disorders Cytokine release syndrome	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
General disorders Fatigue	12.8% 5/39 • Number of events 5 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	16.2% 6/37 • Number of events 6 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
General disorders Fever Without Neutropenia	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	8.1% 3/37 • Number of events 3 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
General disorders Flu-Like Syndrome	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Reproductive system and breast disorders Gynecomastia	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Investigations Hemoglobin Increased	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Blood and lymphatic system disorders Leukocytosis	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Psychiatric disorders Mood Alteration	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Respiratory, thoracic and mediastinal disorders Mucositis	5.1% 2/39 • Number of events 2 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	8.1% 3/37 • Number of events 3 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Gastrointestinal disorders Nausea	12.8% 5/39 • Number of events 5 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	13.5% 5/37 • Number of events 5 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Investigations Neutrophil count decreased	5.1% 2/39 • Number of events 2 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Musculoskeletal and connective tissue disorders Pain (Back)	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	5.4% 2/37 • Number of events 2 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Musculoskeletal and connective tissue disorders Pain (Extremity-Limbs)	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
General disorders Pain (Face)	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Musculoskeletal and connective tissue disorders Pain (Joint)	2.6% 1/39 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	0.00% 0/37 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.
Gastrointestinal disorders Vomiting	0.00% 0/39 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.	2.7% 1/37 • Number of events 1 • Adverse event collection from beginning of treatment through week 21, and up to week 24 post treatment. Three of the 40 participants in the Non-Strontium arm (Arm 2) did not receive treatment and are therefore excluded from Adverse Event reporting.