Hormonal Therapy and Chemotherapy Followed by Prostatectomy in Patients With Prostate Cancer

• Sponsor: The University of Texas Health Science Center, Houston (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02494713
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 23.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a study for men who have locally-advanced prostate cancer and are eligible to undergo prostatectomy. Standard treatment is prostatectomy alone, but there is a chance that cancer may spread to other organs in the future, even after the prostate is removed. If this were to occur, standard treatment would be androgen deprivation therapy (ADT; hormone therapy that blocks testosterone) plus chemotherapy. Clinical trials suggest that neoadjuvant treatment (treatment given before primary therapy) may prevent a recurrence. The purpose of this research study is to assess the safety and benefit of ADT plus chemotherapy given before prostate removal.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Degarelix; Drug: Doxorubicin; Drug: Ketoconazole; Drug: Docetaxel; Drug: Estramustine	Phase 2

Detailed Description

This is an open-label, single-arm study of neoadjuvant ADT and chemotherapy in subjects with non-metastatic, locally-advanced prostate cancer who are eligible for radical prostatectomy.

Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy. Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy.

The primary endpoint will be complete or near-complete pathologic response.

Safety will be assessed on any patient receiving at least one dose of study drug by the reporting of adverse events, vital signs and by the assessment of findings on physical exam and routine safety laboratory determinations. The severity of adverse events and certain abnormal laboratory findings will be assessed according to the NCI CTCAE V4.03.

Laboratory-based studies will evaluate the following:

• Complete metabolic profile

o BUN, creatinine, alkaline phosphatase, ALT/AST, total bilirubin, LDH, calcium, albumin, glucose, magnesium, uric acid, phosphorous

• Electrolytes

o Sodium, potassium, chloride, CO2 content

• Hematology

• CBC with differential, platelet count

• PT, INR, PTT

• Testosterone

• Biomarkers

• PSA

• CTCs

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant Androgen Deprivation Therapy and Chemotherapy Followed by Radical Prostatectomy in Patients With Prostate Cancer
• Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Sep 14, 2017
• Actual Study Completion Date: Sep 14, 2017

Arms and Interventions

Arm

Intervention/Treatment

Other: ADT + chemotherapy Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy.

Drug: Degarelix; Subcutaneous injection, once/month for 4 months; Other Names: Firmagon degarelix acetate ; Drug: Doxorubicin; 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5; Other Names: Adriamycin ; Drug: Ketoconazole; 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5; Other Names: Nizoral ; Drug: Docetaxel; 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6; Other Names: Taxotere ; Drug: Estramustine; 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6; Other Names: Emcyt

Outcome Measures

Primary Outcome Measures

1. Efficacy as Measured by Pathologic Response [Day of prostate removal, which is about 5 months following the day participant signed consent.]

   Pathologic response is defined by percentage of tumor burden remaining at time of prostate removal. Percentage of tumor burden is measured based on a pathologist's assessment of the prostate tissue removed and visual estimate of how much tumor there is in the prostate.

Secondary Outcome Measures

1. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [baseline]

   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.

2. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [Cycle 2 Day 1, about 8 weeks after treatment initiation (but before prostatectomy)]

   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.

3. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [Cycle 2 Day 57, about 16 weeks after treatment initiation (but before prostatectomy)]

   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.

4. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [Day 133, about 19 weeks after treatment initiation (but before prostatectomy)]

   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.

5. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [about 20 weeks after treatment initiation (day of prostatectomy)]

   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.

6. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [about 32 weeks after treatment initiation (about 12 weeks after prostatectomy)]

   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.

7. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [about 44 weeks after treatment initiation (about 24 weeks after prostatectomy)]

   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.

8. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [about 68 weeks after treatment initiation (about 48 weeks after prostatectomy)]

   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.

9. Efficacy as Measured by Circulating Tumor Cell (CTC) Numbers [From the time the participant signs the informed consent until prostatectomy, an average of 5 months.]

10. Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI) [baseline]

    The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging.

11. Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI) [post treatment but prior to prostatectomy (about 25 days after the end of treatment)]

    The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging.

12. Safety of Drug Regimen as Measured by Number of Adverse Events [From the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy.]

    Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy.

13. Surgical Morbidity as Measured by Number of Adverse Events [From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 20 months]

    Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until the participant was taken off-study or the study was stopped, an average of 20 months

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Pathologic proof of prostatic adenocarcinoma without evidence of regional and/or distant metastasis, clinical stage T1c or T2a with high grade disease (Gleason 8-10) on initial biopsy, clinical stage T2b-T2c with Gleason grade 7 (4+3), or clinical stage T3. No neuroendocrine differentiation or small cell features.

• Recent (<6 weeks prior to study entry) negative bone scan and CT of the chest and abdomen.

• Appropriate surgical candidate for radical prostatectomy and a performance status of <2 (ECOG scale).

• Adequate bone marrow function as defined as an absolute peripheral granulocyte count

1500 and platelet count >100,000.

• Adequate hepatic function per the following criteria:

• Albumin ≥2.8 g/dL

• AST and ALT ≤5 x ULN

• Total bilirubin <2 mg/dL

• Adequate renal function per the following criteria:

o Serum creatinine ≤1.5 x ULN

• Normal coagulation profile (INR ≤ 1.5, aPTT ≤ 1.5 x ULN for the lab) and no history of substantial non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only (for control of central line patency).

• Age ≥ 18 years

• Written informed consent to participate in this study.

Exclusion Criteria:

• Prostatic adenocarcinoma with neuroendocrine differentiation or small cell features

• Surgical resection or major surgery within 4 weeks or stereotactic biopsy within 1 week of first ADT and chemotherapy treatment

• Previous or current hormonal treatment, chemotherapy, radiation therapy, immunotherapy, or investigational study drug.

• Unable to tolerate multiparametric MRI or is contraindicated.

• Patients not appropriate surgical candidates for radical prostatectomy based on the evaluation of coexistent medical diseases and competing causes of death.

• Patients with uncontrolled cardiac, hepatic, renal, or neurologic/psychiatric disorder.

• Severe gastrointestinal bleeding within 12 weeks of treatment with ADT and chemotherapy

• Patients who are HIV positive or have chronic hepatitis B or C infections.

• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless a 2D echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months of enrollment demonstrates a left ventricular ejection fraction >45%.

• Sensory neuropathy grade >1.

• History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer.

• Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment.

• Any other condition, including concurrent medical condition, social circumstance or drug dependency, which in the opinion of the investigator could compromise patient safety and/or compliance with study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UTHealth Memorial Hermann Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• The University of Texas Health Science Center, Houston

Investigators

• Principal Investigator: Robert J Amato, D.O., The University of Texas Health Science Center, Houston

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 21, 2016

More Information

Publications

None provided.

• Responsible Party: Robert J Amato, Professor and Director, Division of Oncology, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT02494713
• Other Study ID Numbers: GU-14-101; HSC-MS-14-0424
• First Posted: Jul 10, 2015
• Last Update Posted: Nov 27, 2018
• Last Verified: Nov 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Robert J Amato, Professor and Director, Division of Oncology, The University of Texas Health Science Center, Houston: Advanced Prostate Cancer; Neoadjuvant; Hormone therapy; ADT; Androgen Deprivation Therapy; Chemotherapy; Radical Prostatectomy
• Additional relevant MeSH terms: Prostatic Neoplasms; Ketoconazole; Docetaxel; Doxorubicin; Estramustine

Study Results

Participant Flow

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Period Title: Overall Study
STARTED	4
COMPLETED	4
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Overall Participants	4
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	4 100%
Race/Ethnicity, Customized (Count of Participants)
White	4 100%
Region of Enrollment (Count of Participants)
United States	4 100%
ECOG Performance Status (Count of Participants)
0	4 100%
1	0 0%
2	0 0%
3	0 0%
4	0 0%
5	0 0%

Outcome Measures

1. Primary Outcome

Title	Efficacy as Measured by Pathologic Response
Description	Pathologic response is defined by percentage of tumor burden remaining at time of prostate removal. Percentage of tumor burden is measured based on a pathologist's assessment of the prostate tissue removed and visual estimate of how much tumor there is in the prostate.
Time Frame	Day of prostate removal, which is about 5 months following the day participant signed consent.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [percentage of tumor burden remaining]	30

2. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [ng/mL]	58.7

3. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	Cycle 2 Day 1, about 8 weeks after treatment initiation (but before prostatectomy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [ng/mL]	0.4

4. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	Cycle 2 Day 57, about 16 weeks after treatment initiation (but before prostatectomy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [ng/mL]	0.15

5. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	Day 133, about 19 weeks after treatment initiation (but before prostatectomy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [ng/mL]	0.055

6. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	about 20 weeks after treatment initiation (day of prostatectomy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [ng/mL]	0.01

7. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	about 32 weeks after treatment initiation (about 12 weeks after prostatectomy)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [ng/mL]	0.01

8. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	about 44 weeks after treatment initiation (about 24 weeks after prostatectomy)

Outcome Measure Data

Analysis Population Description

This data was only collected for 3 out of the 4 participants.

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	3
Median (Full Range) [ng/mL]	0.35

9. Secondary Outcome

Title	Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Description	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.
Time Frame	about 68 weeks after treatment initiation (about 48 weeks after prostatectomy)

Outcome Measure Data

Analysis Population Description

This data was collected for only 3 out of the 4 participants.

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	3
Median (Full Range) [ng/mL]	0.1

10. Secondary Outcome

Title	Efficacy as Measured by Circulating Tumor Cell (CTC) Numbers
Time Frame	From the time the participant signs the informed consent until prostatectomy, an average of 5 months.

Outcome Measure Data

Analysis Population Description

This data was not collected for any participants.

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	0

11. Secondary Outcome

Title	Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI)
Description	The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging.
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [cc]	19.3

12. Secondary Outcome

Title	Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI)
Description	The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging.
Time Frame	post treatment but prior to prostatectomy (about 25 days after the end of treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Median (Full Range) [cc]	3.75

13. Secondary Outcome

Title	Safety of Drug Regimen as Measured by Number of Adverse Events
Description	Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy.
Time Frame	From the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Number [adverse event]	119

14. Secondary Outcome

Title	Surgical Morbidity as Measured by Number of Adverse Events
Description	Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until the participant was taken off-study or the study was stopped, an average of 20 months
Time Frame	From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 20 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Measure Participants	4
Number [adverse event]	119

Adverse Events

Time Frame	From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 20 months.
Arm/Group Title	ADT + Chemotherapy
Arm/Group Description	Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy. Degarelix: Subcutaneous injection, once/month for 4 months Doxorubicin: 20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5 Ketoconazole: 400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5 Docetaxel: 35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6 Estramustine: 280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
All Cause Mortality
	ADT + Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	ADT + Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Other (Not Including Serious) Adverse Events
	ADT + Chemotherapy
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Eye disorders
WATERY EYES	1/4 (25%)	1
Gastrointestinal disorders
BLOATING	2/4 (50%)	6
CONSTIPATION	3/4 (75%)	3
DIARRHEA	2/4 (50%)	4
DRY MOUTH	1/4 (25%)	2
DYSPEPSIA	1/4 (25%)	1
GASTROESOPHAGEAL REFLUX	2/4 (50%)	9
NAUSEA	3/4 (75%)	5
Vomiting	1/4 (25%)	1
General disorders
BACK PAIN	1/4 (25%)	2
EDEMA LIMBS	3/4 (75%)	9
FATIGUE	4/4 (100%)	12
FLU LIKE SYMPTOM-ACHINESS	1/4 (25%)	1
INJECTION SITE REACTION	2/4 (50%)	3
MALAISE	1/4 (25%)	2
NON-CARDIAC CHEST PAIN	1/4 (25%)	1
PAIN	2/4 (50%)	3
Infections and infestations
INFECTIONS/INFESTATIONS, THRUSH	1/4 (25%)	1
Injury, poisoning and procedural complications
BRUISING - PORT A CATH SITE	2/4 (50%)	2
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/4 (25%)	1
Metabolism and nutrition disorders
HYPOPHOSPHATEMIA	3/4 (75%)	6
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL/CONNECTIVE TISSUE DISORDERS, MUSCLE ACHES	1/4 (25%)	2
MYALGIA	1/4 (25%)	1
GENERALIZED MUSCLE WEAKNESS	1/4 (25%)	1
Nervous system disorders
COGNITIVE DISTURBANCE	1/4 (25%)	1
DIZZINESS	2/4 (50%)	2
DYSGEUSIA	2/4 (50%)	4
HEADACHE	1/4 (25%)	1
Psychiatric disorders
AGITATION	1/4 (25%)	1
INSOMNIA	2/4 (50%)	5
PSYCHIATRIC DISORDER, EMOTIONAL	1/4 (25%)	2
RESTLESSNESS	1/4 (25%)	1
PSYCHIATRIC DISORDER, ANGER	1/4 (25%)	1
Reproductive system and breast disorders
BREAST PAIN	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
COUGH	2/4 (50%)	2
HICCUPS	1/4 (25%)	1
NASAL CONGESTION	1/4 (25%)	1
POST NASAL DRIP	2/4 (50%)	3
SNEEZING	1/4 (25%)	1
Skin and subcutaneous tissue disorders
ALOPECIA	4/4 (100%)	4
BULLOUS DERMATITIS	1/4 (25%)	1
DRY SKIN	1/4 (25%)	1
NAIL DISCOLORATION	1/4 (25%)	1
SKIN/SQ TISSUE DISORDERS, PEELING OF SKIN AT PORT A CATH SITE	1/4 (25%)	1
SKIN/SQ TISSUE DISORDERS, RIGHT HAND SKIN IRRITATION	2/4 (50%)	2
Vascular disorders
FLUSHING	1/4 (25%)	1
HOT FLASHES	2/4 (50%)	2

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed and limited data.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.