Docetaxel Followed by Radical Prostatectomy in Patients With High Risk Localized Prostate Cancer

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01250717
• Collaborator: Walter Reed Army Medical Center (U.S. Fed)
• Enrollment: 28
• Location: 1
• Arm: 1
• Duration (Months): 123.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine if the combination of chemotherapy and hormone therapy is safe and helpful for patients who plan to have their high-risk prostate cancer surgically removed. Some physicians believe that patients with high risk cancer that is located in one area, may have an early but small spread of the cancer outside of the prostate, and perhaps even to distant organs. Therefore, better treatments for the entire body are needed to improve the ability of surgery or other local therapies to cure prostate cancer. Since chemotherapy is beginning to demonstrate increasing activity in advanced prostate cancer patients, it is possible that using chemotherapy combined with hormonal therapy earlier in the course of localized but high risk patients might improve the outcomes for these patients.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Docetaxel; Drug: Dexamethasone; Drug: Estramustine; Drug: Zoladex; Drug: Casodex; Procedure: Radical Prostatectomy	Phase 2

Detailed Description

• Participants will receive treatment in the outpatient clinic, where the docetaxel chemotherapy will be placed in a bag of fluid and will be given by vein every three weeks. Participants will take Decadron (dexamethasone) by mouth 12 hours and 1 hour before docetaxel and again 12 hours after docetaxel. They will also take estramustine and casodex by mouth at home. Zoladex (or lupron) will be given subcutaneously (under the skin) 4 times every three months. They will also be started on coumadin beginning at the time of the first docetaxel infusion and continuing until 3 weeks after the 4th cycle of chemotherapy.

• After 2 months (or cycles) of therapy, participants will be evaluated in order to assess the response and toxicity of treatment, including a review of medical history, physical examination, blood tests, including PSA. If there is no evidence of progression or excessive toxicity, treatment will continue for 2 more months in the same manner.

• At the end of 4 months of chemotherapy, participants will be reassessed by the medical oncologist and urologist regarding surgery to remove the prostate.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Docetaxel Followed by Radical Prostatectomy in Patients With High Risk Localized Prostate Cancer
• Study Start Date: Jan 1, 2001
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Docetaxel Followed by Radical Prostatectomy Docetaxel,Dexamethasone,Estramustine,Zoladex,Casodex,Prostatectomy

Drug: Docetaxel; Given by an IV infusion over 1 hour on day 2 of a three-week cycle; Other Names: Taxotere ; Drug: Dexamethasone; Orally 12 hours and 1 hour before docetaxel and again 12 hours after docetaxel; Other Names: Decadron ; Drug: Estramustine; Taken orally three times a day for 5 days for the first part of every three week cycle; Drug: Zoladex; Given subcutaneously for 4 doses every three months; Other Names: goserelin acetate ; Drug: Casodex; Taken orally once a day for 6 months; Other Names: Bicalutamide ; Procedure: Radical Prostatectomy; after the chemo and hormonal therapy all patients have a radiacal prostatectomy

Outcome Measures

Primary Outcome Measures

1. Pathologic Complete Response Was Assessed by Rigorous Pathological Examination by One of Two Pathologists [status post prostectomy]

   One of two pathologists (SR, EG), assigned the Gleason scores for each patient from pre-treatment prostate biopsies and assessed pathological staging on post- prostatectomy specimens. Staging including a description of all tumor foci within the gland, presence or absence of perineural invasion and/or lymphovascular invasion, presence of extraprostatic extension of tumor (including seminal vesicle invasion), and margin status. The pathologists reviewed the presence or absence of cancer in each prostate gland removed on the study patients. RECIST has to my knowledge not been used for pathological examination in neoadjuvant studies. 0 out of 28 participants acheived complete response. RECIST is not appropriate as cancer within the gland at the time of treatment is not measurable by RECIST. The primary outcome is a pathological complete response.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the prostate

• Potential candidate for radical prostatectomy

• Any of the following: a) clinical stage T3 patients, b) Serum PSA greater than or equal to 20 ng/ml, c) Gleason score 8-10, d) Clinical T2 disease and either MRI evidence of seminal vesicle involvement or Gleason 4+3 cancer with either 5 or 6 biopsies positive

• ECOG Performance Status 0-1

• WBC > 3,000 ul

• HCT > 30%

• PLT > 100,000/ul

• LFTS within normal limits

Exclusion Criteria:

• Prior hormones, radiation or chemotherapy for prostate cancer

• Myocardial infarction within 1 year, significant change in anginal pattern within last 6 months, current congestive heart failure (NYHA Class 2 or higher), or deep venous thrombosis within 1 year

• Evidence of active infection

• Significant peripheral neuropathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Walter Reed Army Medical Center

Investigators

• Principal Investigator: Glenn J. Bubley, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Glenn Bubley, MD, Director Of Genitourinary Oncology @ Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01250717
• Other Study ID Numbers: 2001P-001577; E-99-0363-FB
• First Posted: Dec 1, 2010
• Last Update Posted: Feb 4, 2014
• Last Verified: Aug 1, 2012

• Keywords provided by Glenn Bubley, MD, Director Of Genitourinary Oncology @ Beth Israel Deaconess Medical Center, Dana-Farber Cancer Institute: prostatectomy; docetaxel
• Additional relevant MeSH terms: Prostatic Neoplasms; Dexamethasone; Goserelin; Estramustine; Docetaxel; Bicalutamide

Study Results

Participant Flow

Recruitment Details	Between September 28, 1999 and May 17, 2005, 28 participants with high risk localized prostate cancer were enrolled on this IRB approved phase II protocol from BIDMC Urology clinics
Pre-assignment Detail	This was a single arm study and there were no arms. Participants were screened for final eligibility after consent was completed. All enrolled subjects were treated

Arm/Group Title	Docetaxel Followed by Radical Prostatectomy
Arm/Group Description	This is a single arm study and there were no arms other than the one arm. All participants were treated according to the regimen below. Docetaxel Followed by Radical Prostatectomy Radical Prostatectomy : after the chemo and hormonal therapy all patients have a radical prostatectomy Zoladex : Given subcutaneously for 4 doses every three months Casodex : Taken orally once a day for 6 months Estramustine : Taken orally three times a day for 5 days for the first part of every three week cycle Docetaxel : Given by an IV infusion over 1 hour on day 2 of a three-week cycle Dexamethasone : Orally 12 hours and 1 hour before docetaxel and again 12 hours after docetaxel
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Docetaxel Followed by Radical Prostatectomy
Arm/Group Description	This is a single arm study and there were no arms other than the one arm. All participants were treated according to the regimen below. Docetaxel Followed by Radical Prostatectomy Radical Prostatectomy : after the chemo and hormonal therapy all patients have a radical prostatectomy Zoladex : Given subcutaneously for 4 doses every three months Casodex : Taken orally once a day for 6 months Estramustine : Taken orally three times a day for 5 days for the first part of every three week cycle Docetaxel : Given by an IV infusion over 1 hour on day 2 of a three-week cycle Dexamethasone : Orally 12 hours and 1 hour before docetaxel and again 12 hours after docetaxel
Overall Participants	28
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	28 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	57 (NA)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	28 100%
Region of Enrollment (participants) [Number]
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	Pathologic Complete Response Was Assessed by Rigorous Pathological Examination by One of Two Pathologists
Description	One of two pathologists (SR, EG), assigned the Gleason scores for each patient from pre-treatment prostate biopsies and assessed pathological staging on post- prostatectomy specimens. Staging including a description of all tumor foci within the gland, presence or absence of perineural invasion and/or lymphovascular invasion, presence of extraprostatic extension of tumor (including seminal vesicle invasion), and margin status. The pathologists reviewed the presence or absence of cancer in each prostate gland removed on the study patients. RECIST has to my knowledge not been used for pathological examination in neoadjuvant studies. 0 out of 28 participants acheived complete response. RECIST is not appropriate as cancer within the gland at the time of treatment is not measurable by RECIST. The primary outcome is a pathological complete response.
Time Frame	status post prostectomy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel Followed by Radical Prostatectomy
Arm/Group Description	This is a single arm study and there were no arms other than the one arm. All participants were treated according to the regimen below. Docetaxel Followed by Radical Prostatectomy Radical Prostatectomy : after the chemo and hormonal therapy all patients have a radical prostatectomy Zoladex : Given subcutaneously for 4 doses every three months Casodex : Taken orally once a day for 6 months Estramustine : Taken orally three times a day for 5 days for the first part of every three week cycle Docetaxel : Given by an IV infusion over 1 hour on day 2 of a three-week cycle Dexamethasone : Orally 12 hours and 1 hour before docetaxel and again 12 hours after docetaxel
Measure Participants	28
Number [participants]	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel Followed by Radical Prostatectomy
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; 0 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 months
Adverse Event Reporting Description	followed for four cycles of therapy
Arm/Group Title	Docetaxel Followed by Radical Prostatectomy
Arm/Group Description	This is a single arm study and there were no arms other than the one arm. All participants were treated according to the regimen below. Docetaxel Followed by Radical Prostatectomy Radical Prostatectomy : after the chemo and hormonal therapy all patients have a radical prostatectomy Zoladex : Given subcutaneously for 4 doses every three months Casodex : Taken orally once a day for 6 months Estramustine : Taken orally three times a day for 5 days for the first part of every three week cycle Docetaxel : Given by an IV infusion over 1 hour on day 2 of a three-week cycle Dexamethasone : Orally 12 hours and 1 hour before docetaxel and again 12 hours after docetaxel
All Cause Mortality
	Docetaxel Followed by Radical Prostatectomy
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Docetaxel Followed by Radical Prostatectomy
	Affected / at Risk (%)	# Events
Total	5/28 (17.9%)
Blood and lymphatic system disorders
neutropenic fever	4/28 (14.3%)	4
Hepatobiliary disorders
elevated liver functions	1/28 (3.6%)	1
Other (Not Including Serious) Adverse Events
	Docetaxel Followed by Radical Prostatectomy
	Affected / at Risk (%)	# Events
Total	0/28 (0%)

Limitations/Caveats

Although this study has the longest median follow-up periods reported (80 months or 6.6 years), the overall number of participants is too few to make strong judgements about efficacy

More Information

Certain Agreements

Principal Investigators are NOT 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.