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Summary

for males ages 18 years and up (full criteria)
at San Francisco, California and other locations
study started

Description

Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as flutamide, bicalutamide, and luteinizing hormone-releasing hormone agonist, may lessen the amount of androgens made by the body. It is not yet known which regimen of radiation therapy with or without androgen-deprivation therapy is more effective for prostate cancer.

PURPOSE: This randomized phase III trial is studying prostate radiation therapy to see how well it works compared with short-term androgen deprivation therapy given together with pelvic lymph node radiation therapy with or without prostate radiation therapy in treating patients with a rising PSA after surgery for prostate cancer.

Official Title

A Phase III Trial of Short Term Androgen Deprivation With Pelvic Lymph Node or Prostate Bed Only Radiotherapy (SPPORT) in Prostate Cancer Patients With a Rising PSA After Radical Prostatectomy

Details

OBJECTIVES:

Primary

  • To determine whether the addition of short-term androgen deprivation (STAD) to prostate bed radiotherapy (PBRT) improves freedom from progression (FFP) (i.e., maintenance of a prostate-specific antigen [PSA] less than the nadir+2 ng/mL, absence of clinical failure, and absence of death from any cause) for 5 years, over that of PBRT alone in men treated with salvage radiotherapy after radical prostatectomy.
  • To determine whether STAD, pelvic lymph node radiotherapy (PLNRT), and PBRT improves FFP over that of STAD+PBRT and PBRT alone in men treated with salvage radiotherapy after radical prostatectomy.

Secondary

  • To compare the rates of a PSA ≥ 0.4 ng/mL and rising at 5 years after randomization (secondary biochemical failure endpoint), the development of hormone-refractory disease (3 rises in PSA during treatment with salvage androgen-deprivation therapy), distant metastasis, cause-specific mortality, and overall mortality.
  • To compare acute and late morbidity based on Common Toxicity Criteria for Adverse Effects (CTCAE), v. 3.0.
  • To measure the expression of cell kinetic, apoptotic pathway, and angiogenesis-related genes in archival diagnostic tissue to better define the risk of FFP, distant failure, cause-specific mortality, and overall mortality after salvage radiotherapy for prostate cancer, independently of conventional clinical parameters now used.
  • To quantify blood product-based proteomic and genomic (single nucleotide polymorphisms) patterns and urine-based genomic patterns before and at different times after treatment to better define the risk of FFP, distant failure, cause-specific mortality, and overall mortality after salvage radiotherapy for prostate cancer, independently of conventional clinical parameters now used.
  • To assess the degree, duration, and significant differences of disease-specific health-related quality of life (HRQOL) decrements among treatment arms.
  • To assess whether mood is improved and depression is decreased with the more aggressive therapy if it improves FFP.
  • To collect paraffin-embedded tissue blocks, serum, plasma, urine, and buffy coat cells for future translational research analyses.

Tertiary

  • To assess whether an incremental gain in FFP and survival with more aggressive therapy outweighs decrements in the primary generic domains of HRQOL (i.e., mobility, self care, usual activities, pain/discomfort, and anxiety/depression).
  • To evaluate the cost-utility of the treatment arm demonstrating the most significant benefit (in terms of the primary outcome) in comparison with other widely accepted cancer and non-cancer therapies.
  • To assess associations between serum levels of beta-amyloid and measures of cognition and mood and depression.
  • An exploratory aim is to assess the relationship(s) between the American Urological Association Symptom Index (AUA SI) and urinary morbidity using the CTCAE v. 3.0 grading system.

OUTLINE: Patients are stratified according to seminal vesicle involvement (yes vs no), prostatectomy Gleason score (≤ 7 vs 8-9), pre-radiotherapy PSA (≥ 0.1 and ≤ 1.0 ng/mL vs > 1.0 and < 2.0 ng/mL), and pathology stage (pT2 and margin negative vs all others). Patients are randomized to 1 of 3 treatment arms.

  • Arm I (prostate bed radiotherapy [PBRT] alone): Patients undergo PBRT once daily, 5 days a week, Monday through Friday, for approximately 7-8 weeks (36 to 39 fractions).
  • Arm II (PBRT and short-term androgen-deprivation [STAD]): Beginning 2 months before the start of PBRT, patients undergo STAD, using a combination of antiandrogen and luteinizing hormone-releasing hormone (LHRH) agonist therapy, for a total of 4-6 months. Patients receive antiandrogen therapy comprising either oral flutamide 3 times daily or oral bicalutamide once daily for at least 4 months (started within 1-14 days prior to the LHRH agonist and ending the last day of radiotherapy ± 14 days). Patients receive LHRH agonist injection beginning concurrently with or 2 weeks after the start of antiandrogen therapy. LHRH agonist injection consists of analogs approved by the FDA (or by Health Canada for Canadian institutions) (e.g., leuprolide, goserelin, buserelin, or triptorelin) and may be given in any possible combination (may be given as a single 4-month injection and one to two 1-month injection[s], two 3-month injections, or a 6-month injection), such that the total LHRH agonist treatment time is 4-6 months. Approximately 2 months after beginning of STAD, patients undergo PBRT as in arm I.
  • Arm III (Pelvic lymph node radiotherapy [PLNRT], PBRT, and STAD): Beginning 2 months before the start of radiotherapy, patients receive STAD therapy as in arm II. Approximately 2 months after beginning of STAD, patients undergo PBRT and PLNRT once daily, 5 days a week, Monday through Friday, for approximately 5 weeks (25 fractions) followed by PBRT only once daily, 5 days a week for approximately 2-3 weeks (11-14 fractions).

Patients complete the American Urological Association Symptom Index (AUA SI) questionnaire prior to protocol treatment, at week 6 of radiotherapy, and then periodically after completion of study therapy.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

Keywords

Prostate Cancer stage IIB prostate cancer stage IIA prostate cancer stage III prostate cancer adenocarcinoma of the prostate Prostatic Neoplasms Androgens Bicalutamide Flutamide

Eligibility

For males ages 18 years and up

DISEASE CHARACTERISTICS:

  • 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 (Nx [undissected pelvic lymph nodes because lymph node dissection is not required])
  • Any type of radical prostatectomy allowed, including retropubic, perineal,laparoscopic, or robotically assisted
  • Meets 1 of the following pathologic classifications:
  • T3 N0/Nx disease with or without positive prostatectomy margins
  • T2 N0/Nx disease with or without positive prostatectomy margins
  • 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 negative
  • Prostatectomy Gleason score of 9 or less
  • A post-radical prostatectomy entry PSA of ≥ 0.1 and ≤ 1.0 ng/mL at least 6 weeks after prostatectomy and within 30 days of registration
  • Serum total testosterone ≥ 40% of the lower limit of normal (patients who have had a unilateral orchiectomy are eligible as long as this requirement is met)
  • No distant metastases based on history/physical examination, CT scan or MRI of the abdomen and pelvis, and bone scan
  • No palpable prostatic fossa abnormality/mass suggestive of recurrence, unless shown by biopsy under ultrasound guidance not to contain cancer

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • Platelets ≥ 100,000/mm3

  • Hemoglobin ≥ 10.0 g/dL (the use of transfusion or other intervention to achieve this is allowed)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x upper limit of normal
  • No prior invasive malignancy (except nonmelanoma skin cancer) or superficial bladder cancer unless disease free for a minimum of 5 years (e.g., carcinoma in situ of the oral cavity is permissible)
  • No severe, active co-morbidity, including any of the following:
  • History of inflammatory bowel disease
  • History of hepatitis B or C
  • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  • Transmural myocardial infarction within the past 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition
  • HIV testing is not required for entry
  • No prior allergic reaction to the study drug(s) involved in this protocol

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • More than 5 years since prior chemotherapy for any other disease site
  • No androgen-deprivation therapy started prior to prostatectomy for > 6 months duration
  • The use of finasteride or dutasteride (± tamsulosin) for longer periods prior to prostatectomy is acceptable
  • No androgen-deprivation therapy started after prostatectomy and prior to registration
  • The use of finasteride or dutasteride (± tamsulosin) after prostatectomy is not acceptable, it must be stopped within 3 months after prostatectomy
  • No neoadjuvant chemotherapy before or after prostatectomy
  • No prior cryosurgery or brachytherapy of the prostate (prostatectomy should be the primary treatment and not a salvage procedure)
  • No prior pelvic radiotherapy

Locations

  • UCSF Helen Diller Family Comprehensive Cancer Center
    San Francisco, California, 94115, United States
  • California Pacific Medical Center - California Campus
    San Francisco, California, 94118, United States
  • California Cancer Center - Woodward Park Office
    Fresno, California, 93720, United States
  • Cancer Care Associates
    Fresno, California, 93720, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California, 94609, United States
  • Bay Area Breast Surgeons, Incorporated
    Oakland, California, 94609, United States
  • CCOP - Bay Area Tumor Institute
    Oakland, California, 94609, United States
  • Larry G Strieff MD Medical Corporation
    Oakland, California, 94609, United States
  • Tom K Lee, Incorporated
    Oakland, California, 94609, United States
  • Peninsula Medical Center
    Burlingame, California, 94010, United States
  • Doctors Medical Center - San Pablo Campus
    San Pablo, California, 94806, United States
  • East Bay Radiation Oncology Center
    Castro Valley, California, 94546, United States
  • Valley Medical Oncology Consultants - Castro Valley
    Castro Valley, California, 94546, United States
  • Contra Costa Regional Medical Center
    Martinez, California, 94553-3156, United States
  • Sutter Health - Western Division Cancer Research Group
    Novato, California, 94945, United States
  • Sutter Solano Medical Center
    Vallejo, California, 94589, United States
  • Valley Medical Oncology
    Fremont, California, 94538, United States
  • Washington Township Hospital
    Fremont, California, 94538, United States
  • El Camino Hospital Cancer Center
    Mountain View, California, 94040, United States
  • Solano Radiation Oncology Center
    Vacaville, California, 95687, United States
  • Saint Helena Hospital
    Saint Helena, California, 94574, United States
  • University of California Davis Cancer Center
    Sacramento, California, 95817, United States
  • Mercy General Hospital
    Sacramento, California, 95819, United States
  • Radiological Associates of Sacramento Medical Group, Incorporated
    Sacramento, California, 95815, United States
  • Memorial Medical Center
    Modesto, California, 95355, United States
  • Mercy Cancer Center at Mercy San Juan Medical Center
    Carmichael, California, 95608, United States
  • Radiation Oncology Center - Roseville
    Roseville, California, 95661, United States
  • Radiation Oncology Centers - Cameron Park
    Cameron Park, California, 95682, United States
  • Auburn Radiation Oncology
    Auburn, California, 95603, United States
  • Enloe Cancer Center at Enloe Medical Center
    Chico, California, 95926, United States
  • Feather River Hospital Cancer Center
    Paradise, California, 95969, United States
  • Providence Holy Cross Cancer Center
    Mission Hills, California, 91346-9600, United States
  • Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
    Los Angeles, California, 90048, United States
  • USC/Norris Comprehensive Cancer Center and Hospital
    Los Angeles, California, 90089-9181, United States
  • Veterans Affairs Medical Center - Long Beach
    Long Beach, California, 90822, United States
  • St. Joseph Hospital Regional Cancer Center - Orange
    Orange, California, 92868, United States
  • CCOP - Nevada Cancer Research Foundation
    Las Vegas, Nevada, 89106, United States

Details

Status
in progress, not accepting new patients
Start Date
Sponsor
Radiation Therapy Oncology Group
ID
NCT00567580
Phase
Phase 3
Lead Scientist
Mack Roach
Study Type
Interventional
Last Updated
September 2016