Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Supportive care, Treatment||Closed||18 and over||NCI, Other||RTOG 0534|
CDR0000577574, NCI-2009-00733, NCT00567580
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.
Further Study Information
- 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.
- 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.
- 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.
- 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
- Zubrod performance status 0-1
- 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
Trial Lead Organizations/Sponsors
Radiation Therapy Oncology Group
- National Cancer Institute
- Cancer and Leukemia Group B
- NRG Oncology
Alan Pollack, Principal Investigator
Leonard G. Gomella, Study Chair
Joycelyn L. Speight, Study Chair
Virginia K. Crosson Cancer Center at St. Jude Medical Center
William Eyre Lawler
Saint Helena Hospital
David J Tate
Kaiser Permanente Medical Center - Santa Clara Homestead Campus
Louisville Oncology at Norton Cancer Institute - Louisville
Aaron C Spalding
Norton Suburban Hospital
Aaron C Spalding
Shore Regional Cancer Center at Memorial Hospital - Easton
John Philip Mastandrea
CCOP - Montana Cancer Consortium
Benjamin Thomas Marchello
Fred and Pamela Buffett Cancer Center
Andrew O Wahl
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
AnMed Cancer Center
Patricia C Griffin
Harrison Medical Center
Stephen C Springate
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00567580
ClinicalTrials.gov processed this data on April 09, 2015
Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain
the same text. Minor
changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and
contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should
be directed to ClinicalTrials.gov.