Adult Clinical Trials: GENITOURINARY & PROSTATE

RTOG 0232: PROSTATE

A Phase III Study Comparing Combined External Beam Radiation And Transperineal Interstitial Permanent Brachytherapy With Brachytherapy Alone For Selected Patients With Intermediate Risk Prostatic Carcinoma

• Histologically confirmed, locally confined adenocarcinoma of the prostate.
• Clinical stages T1c-T2b.
• Zubrod 0-1.
• Combined Gleason 7 if PSA < 10, combined Gleason < 7 if PSA 10-20; PSA must be < 20ng/mL, before hormone therapy, if given (if Gleason 2-6, then PSA must be > 10 ng/mL; Prostate volume by TRUS < 60 cc.
• No prior chemotherapy, pelvic radiation, no prior TURP, cryosurgery, TUNA, TUMT or radical surgery for carcinoma of the prostate.
• No previous hormonal therapy beginning < 2 months or > 6 months prior to registration
• No distant metastases, no clinically or pathologically involved lymph nodes.
• No significant obstructive symptoms.
• AUA must be < 15 (alpha blockers allowed).
• No major medical or psychiatric illness.

Treatment

Arm 1: 45 Gy EBRT, partial pelvis (1.8 Gy/fraction M-F for 5 weeks) followed 2-4 weeks later by Pd-103 (100 Gy) or I-125 (110 Gy)*

Arm 2: Pd-103 (125 Gy) or I-125 (145 Gy)*
*Protocol treatment must begin within 4 weeks after study entry.

RTOG 0517: BREAST, LUNG, AND PROSTATE

Randomized Phase III Trial to Evaluate Radiopharmaceuticals and Zoledronic Acid in the Palliation of Osteoblastic Metastases from Lung, Breast, and Prostate Cancer

• Histologically or cytologically proven diagnosis of solid tumor malignancy of lung, breast, or prostate prior to registration; appropriate diagnosis for protocol entry, based upon the diagnostic workup specified in the protocol
• 18 years of age; Zubrod performance status 0-2 for patients with breast or prostate primaries; Zubrod performance status 0-1 for patients with lung primaries
• Pregnancy test for women of childbearing potential within 2 weeks prior to registration
• All bisphosphonates other than the study drug must be discontinued prior to registration;
• patients with brain metastases and/or spinal cord compression are excluded
• Patients with painful bone metastases are not permitted until these bone metastases are successfully treated (for example by external beam irradiation) prior to registration, and the patient has stable pain for at least 2 weeks after that treatment
• No evidence in the six months prior to study entry of uncontrolled congestive heart failure, hypertension refractory to treatment, or symptomatic coronary artery disease
• No current, active dental problems within 4 weeks of registration, including infection of the teeth or jawbone (maxilla or mandible); dental or fixture trauma; current or prior diagnosis of osteonecrosis of the jaw .

RTOG 0526: GENITOURINARY

A Prospective Phase II Trial Of Transperineal Ultrasound-Guided Brachytherapy For Locally Recurrent Prostate Adenocarcinoma Following External Beam Radiotherapy

Biopsy-documented locally recurrent prostatic adenocarcinoma > 30 months after the completion of EBRT, biopsied 180 days prior to registration and confirmed by central pathology review; Disease-related characteristics at initial diagnosis (i.e., prior to EBRT) that fit one of the following categories (Appendix III):

• Stages T1-T2c, Gleason scores 2-6, and PSA 20 ng/mL, or
• Stages T1-T2c, Gleason score 7, and PSA 10 ng/mL

Staging, performed within 8 weeks prior to registration:

• History/physical examination (to include at a minimum digital rectal examination of the prostate and examination of the skeletal system and abdomen)
• Negative lymph nodes by imaging (pelvic abdominal CT or MR), or by nodal dissection (laparoscopy or laparotomy)
• No evidence of bone metastases (M0) on bone scan

None of the following prior therapies:

• Transurethral resection of the prostate (TURP); Radionuclide (permanent or temporary implantation) prostate brachytherapy ; Prostatectomy or prostatic cryosurgery; HIFU (high-intensity focused ultrasound); Bilateral orchiectomy; Chemotherapy for prostatic carcinoma

• NOTE 1: Androgen suppression therapy is permissible provided that the LHRH agonist was started at least 2 months and no more than 6 months before registration.
  NOTE 2: Any combination of neoadjuvant, concurrent, or adjuvant androgen suppression therapy at the time of initial external radiotherapy is permissible provided the total duration was < 8 months.

Treatment:
PRIOR TO EXTERNAL RADIOTHERAPY
T1-T2c, GS 2-6, PSA < 20 ng/mL
OR
T1-T2c, GS 7, PSA < 10 ng/mL

LOCAL RECURRENCE
>30 months after external radiotherapy
PSA < 10

STEP 1 REGISTER
Central pathology review confirmed

STEP 2 REGISTER
Prostate brachytherapy*

 

RTOG 0534: PROSTATE

Phase III Trial Of Short Term Androgen Deprivation With Pelvic Lymph Node Or Prostate Bed Only Radiotherapy (SPORT) In Prostate Cancer Patients With A Rising PSA After Radical Prostatectomy IN ALL ORDERS GIVEN

• Adenocarcinoma of the prostate treated primarily with radical prostatectomy, pathologically proven to be lymph node negative by pelvic lymphadenectomy (N0) or lymph node status pathologically unknown (undissected pelvic lymph nodes [Nx]), i.e., lymph node dissection is not required;
• Any type of radical prostatectomy will be permitted. If performed, the number of lymph nodes removed per side of the pelvis and the extent of the pelvic lymph node dissection (obturator vs. extended lymph node dissection) should be noted;
• Post-radical prostatectomy entry PSA of > 0.1 and < 2.0 ng/mL at least 6 weeks after prostatectomy and within 30 days of registration;
• One of the following pathologic classifications: T3N0/Nx disease or T2N0/Nx disease with positive prostatectomy margin and/or positive prostatic fossa or urethral-vesical anastomosis biopsies;
• Prostatectomy Gleason score of 9 or less; 
• No distant metastases, based upon the minimum diagnostic workup defined in the protocol;
• AST or ALT < 2 x the upper limit of normal within 90 days prior to registration;
• N1 patients are ineligible, as are those with pelvic lymph node enlargement > 1.5 cm in greatest dimension by CT scan or MRI of the pelvis, unless the enlarged lymph node is sampled and is negative;
• No androgen deprivation therapy started prior to prostatectomy for > 6 months duration;
• No androgen deprivation therapy started after prostatectomy and prior to registration;
• No prior pelvic radiotherapy;

TREATMENT
Arm 1: PBRT Alone*
PBRT 64.8-70.2 Gy

Arm 2: PBRT + NC-STAD
PBRT 64.8-70.2 Gy + NC-STAD for 4-6 months, beginning 2 months before RT

Arm 3: PLNRT + PBRT + NC-STAD
PLNRT to 45 Gy and PBRT to 64.8-70.2 Gy, NC-STAD for 4-6 months, beginning 2 months before RT
 
*SV = seminal vesicle; RT = radiotherapy; PBRT = prostate bed RT; PLNRT = pelvic lymph node RT; NC-STAD = neoadjuvant and concurrent short term androgen deprivatio

RTOG 0612: PROSTATE

Investigating Markers of Radiation Outcome in Patients With Intermediate-Risk Prostate Cancer Using DNA Microarray Analysis: An RTOG Pilot Study

• Patient must be eligible for RTOG 0232.
• Patient must be enrolled on RTOG 0232.
• Submission of the paraffin tissue block from initial diagnosis.
• Submission of the biopsy specimen that contains frozen tissue.
• Patient must sign a study-specific informed consent for RTOG 0612 prior to study entry.

RTOG 0815: PROSTATE

A Phase III Prospective Randomized Trial Of Dose-Escalated Radiotherapy With Or Without Short-Term Androgen Deprivation Therapy For Patients With Intermediate-Risk Prostate Cancer

• Pathologically (histologically) proven diagnosis of prostatic adenocarcinoma within 6 months prior to registration at intermediate risk for recurrence as determined by having one or more of the following intermediate-risk features:
• Gleason Score 7; PSA >10 but <20; Clinical Stage T2b-T2c. Clinically negative lymph nodes as established by imaging (pelvic +/- abdominal CT or MRI), nodal sampling, or dissection within 60 days prior to registration, except as noted in protocol Section 3.1.2.
• No evidence of bone metastases (M0) on bone scan within 60 days prior to registration.
• History/physical examination (to include, at a minimum, digital rectal examination of the prostate and examination of the skeletal system and abdomen, and formal comorbidity assessment via the ACE-27 instrument) within 60 days prior to registration
• Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech) within 60 days prior to registration. Note: Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT; (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasteride.
• CBC/differential obtained within 60 days prior to registration (for patients undergoing brachytherapy only), with adequate bone marrow function as defined in protocol Section 3.1.8. Patient must be able to provide study-specific informed consent prior to study entry.
• No patients with all three intermediate risk factors who also have > 50% of the number of their biopsy cores positive for cancer are ineligible for this trial.
• No prior invasive malignancy (except non-melanomatous skin cancer) or hematological (e.g., leukemia, lymphoma, myeloma) malignancy unless disease free for a minimum of 5 years (prior diagnoses of carcinoma in situ are permitted).
• No prior radical surgery (prostatectomy), high-intensity focused ultrasound (HIFU) or cryosurgery for prostate cancer.
• No prior hormonal therapy, such as LHRH agonists or bilateral orchiectomy.
• No use of finasteride within 30 days prior to registration or use of dutasteride within 90 days prior to registration.
• No prior or concurrent cytotoxic chemotherapy for prostate cancer.
• No prior RT, including brachytherapy, to the region of the study cancer that would result in overlap of RT fields.

Treatment
Stratify by Number of Risk Factors; Comorbidity Status; RT Modality

Arm 1: Dose-escalated RT alone

Arm 2: Dose-escalated RT combined with short-term (6 months) androgen blockade (LHRH agonist + antiandrogen)

RTOG 0831: PROSTATE

A Randomized, Double-Blinded, Placebo-Controlled Phase III Trial To Evaluate The Effectiveness Of A Phosphodiesterase 5 Inhibitor, Tadalafil, In Prevention Of Erectile Dysfunction In Patients Treated With Radiotherapy For Prostate Cancer [Prevention of Erectile Dysfunction Study (PEDS)]

• Clinical stage T1b-T2b (AJCC, 6th ed.) adenocarcinoma of the prostate within 6 months of registration.
• Clinically negative lymph nodes as established by imaging (pelvic abdominal CT or MR), nodal sampling, or dissection within 3 months prior to registration. Patients with lymph nodes equivocal or questionable by imaging are eligible if the nodes are < 1.5 cm.
• Lymph node assessment is optional, and at investigator discretion, for patients with Gleason Score <7.
• No evidence of bone metastases (M0) on bone scan within 3 months prior to registration. Equivocal bone scan findings are allowed if plain films are negative for metastasis. Bone metastases assessment is optional, and at investigator discretion, for patients with Gleason Score <7.
• Baseline serum PSA value performed with an FDA-approved assay (e.g., Abbott, Hybritech) within 3 months prior to registration.
•  Any of the following combinations of factors (Note: tumor found in 1 or both lobes on biopsy, but not palpable, will not alter T stage):
• T1b-T2b disease, Gleason Score <7 and serum total PSA that is <20 ng/ml or
• T1b-T2b disease, Gleason Score >7 and PSA that is <15 ng/ml

Although patients with partners are targeted for recruitment, patients without partners or without partners willing to participate are eligible. Patients (and spouses/partners, if willing to participate) must be able to provide study-specific informed consent.

No use of LHRH agonist androgen suppression (e.g., Lupron, Zoladex), anti-androgen (e.g., Casodex, Eulexin, Nilandron), or estrogenic (e.g., diethylstilbestrol) agents within the last 6 months. No current use of any organic nitrate or as needed nitrates (e.g., use of nitroglycerin) or current use of cimetidine, ketoconazole, itraconazole, erythromycin, or ritonavir. No known moderate to severe renal insufficiency or end-stage renal disease. No known severe hepatic impairment. No use of mechanical (vacuum) devices, intracorporeal, intraurethral, topical, or oral (sildenafil, tadalafil, vardenafil) agents as therapy for ED or supplements to enhance sexual function within 5-7 days prior to the start of RT.
No prior penile implant or history of bilateral orchiectomy. No prior prostatectomy, prostatic cryosurgery or high-intensity focused ultrasound (HIFU), radionuclide prostate brachytherapy, or chemotherapy for prostate cancer. No prior or anticipated combined external RT and brachytherapy. No prior or anticipated external RT to the pelvic ± para-aortic lymph nodes.
Spouse/Partner Eligibility Criteria
A male or female partner is eligible. Spouse/partner must provide signed study-specific informed consent.

Treatment
Stratify:
Age
1. <65 years
2. >65 years

RT Treatment
1. External radiation therapy
2. Brachytherapy

Randomize:
Arm 1: Tadalafil started within 7 days after the start of radiation therapy and continued for 168 days (24 weeks)

Arm 2: Placebo started within 7 days after the start of radiation therapy and continued for 168 days (24 weeks)