Preoperative Radiation Therapy for High Risk Prostate Cancer

A Phase I Dose-Escalation Study of Preoperative Radiation Therapy Followed by Radical Prostatectomy in Patients With High Risk, Localized Carcinoma of the Prostate

This is a Phase I dose-escalation study of moderate dose radiation therapy prior to radical prostatectomy for patients with high-risk localized disease. Its hypothesis is that such treatment will be well tolerated with similar side effect profile as surgery alone. Patients in Groups 1 and 2 will receive 39.6 Gy and 45 Gy (at 1.8 Gy/fx), respectively, to the whole pelvis. Patients in Groups 3 and 4 will receive 45 Gy to the whole pelvis, followed by a boost to the prostate and periprostatic tissue, for total doses of 50.4 and 54 Gy, respectively. The patient will then undergo radical prostatectomy between 4-8 weeks after completion of radiation.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiation; Procedure: Radical Prostatectomy

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Subjects must have

• biopsy-confirmed "high-risk" prostate cancer, defined as A. PSA > 20, B. Gleason Score (GS) >/= 8, and/or C. Clinical stage T3 disease per AJCC Staging Manual, 6th edition; or D. At least two out of three of the following: PSA 10-19.9, GS = 7, or clinical stage = T2b / T2c.
• a negative bone scan,
• be medically fit to undergo surgery as determined by treating urologist,
• age > 18,
• KPS must be >/= 80,
• no prior pelvic radiation therapy, chemotherapy, or androgen deprivation,
• no prior invasive malignancy, except non- melanomatous skin cancer unless disease free for a minimum of 5 years. Carcinoma in-situ of the bladder or head and neck region is permissible.
• Subjects must freely sign informed consent to enroll in the study.

Exclusion Criteria:

• prior pelvic radiation therapy, chemotherapy, or androgen deprivation,
• prior invasive malignancy, except non- melanomatous skin cancer, carcinoma in-situ of the bladder or head and neck region, unless disease free for a minimum of 5 years.
• Metastatic disease as demonstrated by bone scan, CT scan or MRI of the pelvis, or chest x-ray.
• Pathologically documented positive pelvic lymph nodes. If Pre-operative CT scan or MRI (ordered at the discretion of the treating physicians) demonstrates lymph nodes which are suspicious for involvement, then biopsy must be undertaken and nodes proven negative before patient can enroll on this trial.
• Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician.
• History of prior pelvic radiation therapy.
• History of androgen deprivation therapy or chemotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Leve 1 Radiation; Subjects in Group 1 will receive 39.6 Gy (at 1.8 Gy/fx) to the whole pelvis. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation.	Radiation: Radiation; Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes; Procedure: Radical Prostatectomy; Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.
Experimental: Level 2 Radiation; Subjects in Group 2 will receive 45 Gy (at 1.8 Gy/fx) to the whole pelvis. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation.	Radiation: Radiation; Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes; Procedure: Radical Prostatectomy; Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.
Experimental: Level 3 Radiation; Subjects in Group 3 will receive 45 Gy to the whole pelvis, followed by a boost to the prostate and periprostatic tissue, for total doses of 50.4 Gy. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation.	Radiation: Radiation; Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes; Procedure: Radical Prostatectomy; Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.
Experimental: Level 4 Radiation; Subjects in Group 4 will receive 45 Gy to the whole pelvis, followed by a boost to the prostate and periprostatic tissue, for total doses of 54 Gy. The subject will then undergo radical prostatectomy between 4-8 weeks after completion of radiation.	Radiation: Radiation; Pre-operative Radiation to Prostate, SV, and Pelvic Lymph Nodes; Procedure: Radical Prostatectomy; Patients will undergo evaluation by a surgeon for consideration of resection after completion of radiation therapy. If a surgical resection is possible, it is recommended that patients undergo surgery four to eight weeks after completion of radiation therapy. This surgical procedure will be performed by one of the standard accepted approaches.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
post-operative morbidity	30 day

Secondary Outcome Measures

Outcome Measure	Time Frame
continence	1 year
erectile function	1 year
biochemical recurrence	2 years

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Virginia Commonwealth University
• Investigators: Principal Investigator: Bridget F Koontz, MD, Duke University

Publications and helpful links

General Publications

• Koontz BF, Quaranta BP, Pura JA, Lee WR, Vujaskovic Z, Gerber L, Haake M, Anscher MS, Robertson CN, Polascik TJ, Moul JW. Phase 1 trial of neoadjuvant radiation therapy before prostatectomy for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2013 Sep 1;87(1):88-93. doi: 10.1016/j.ijrobp.2013.05.014. Epub 2013 Jun 19.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: December 30, 2009
• First Submitted That Met QC Criteria: December 30, 2009
• First Posted (Estimate): December 31, 2009

Study Record Updates

• Last Update Posted (Estimate): July 17, 2013
• Last Update Submitted That Met QC Criteria: July 16, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: neoadjuvant; radiation; prostatectomy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Pro00006510