Overview

This trial is active, not recruiting.

Condition prostate cancer
Treatments bicalutamide, flutamide, radiation therapy
Phase phase 3
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date February 2008
End date December 2020
Trial size 1792 participants
Trial identifier NCT00567580, CDR0000577574, NCI-2009-00733, NCT01312974, RTOG 0534

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
(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).
radiation therapy
Once daily, 5 days a week
(Experimental)
(PBRT and short-term androgen deprivation [STAD]): Beginning 2 months before the start of PBRT, patients undergo STAD, using a combination of antiandrogen (AA) and LHRH agonist therapy, for a total of 4-6 months. Patients receive AA therapy comprising either oral flutamide 3 times daily or oral bicalutamide once daily for at least 4 months. Patients receive LHRH agonist injection beginning concurrently with or 2 weeks after the start of AA 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.
bicalutamide
Oral, daily
flutamide
Oral, daily
radiation therapy
Once daily, 5 days a week
(Experimental)
(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).
bicalutamide
Oral, daily
flutamide
Oral, daily
radiation therapy
Once daily, 5 days a week

Primary Outcomes

Measure
Freedom from progression (FFP)
time frame: From date of randomization to the first occurrence of biochemical failure by the Phoenix definition (PSA >= 2 ng/ml over the nadir PSA), clinical failure (local, regional or distant) or death from any cause.

Secondary Outcomes

Measure
Secondary biochemical failure
time frame: From date of randomization to a detectable PSA rising for at least two values with the second value at 0.4 ng/mL or greater.
Hormone-refractory disease
time frame: From the date of randomization to the third of three rises of PSA after the institution of salvage hormone therapy.
Local failure
time frame: From the date of randomization to the development of a new palpable abnormality in the prostate bed after enrollment in the protocol.
Distant metastasis
time frame: From randomization to documented (by imaging) distant disease.
Cause-specific mortality
time frame: From date of randomization to the date of death due to prostate cancer.
Overall mortality
time frame: From the date of randomization to the date of death due to any cause.
Incidence of acute adverse events ≤ 90 days of the completion of radiotherapy (RT)
time frame: From the date radiation treatment completion to the first occurrence of worst severity of an adverse event within 90 days.
Time to late grade 2+ and 3+ adverse events assessed > 90 days from the completion of RT
time frame: From date of randomization to the first occurrence of grade 2+ or 3+ adverse event > 90 days after the radiation therapy completion date.
Comparison of disease-specific health related quality of life (HRQOL) change by EPIC, Hopkins Verbal Learning Test Revised (HVLT-R), Trail Making Test, parts A & B, and Controlled Oral Word Association Test (COWAT)
time frame: From the 6th week of radiation therapy to 5 years post radiation therapy.
Assessment of mood and depression change using QOL measured by the Hopkins Symptom Checklist (HSCL-25)
time frame: From the 6th week of radiation therapy to 5 years post radiation therapy.
Assessment and comparison of Quality Adjusted Life Year (QALY) and Quality Adjusted FFP Year (QAFFPY)
time frame: From the 6th week of radiation therapy to 5 years post radiation therapy.
Evaluation and comparison of the cost-utility using EuroQoL - 5 Dimensions (EQ-5D)
time frame: From the 6th week of radiation therapy to 5 years post radiation therapy.
Association between serum levels of beta-amyloid (Abeta) and measures of HSCL-25, the HVLT-R, Trail Making Test, parts A & B, or the COWAT
time frame: From the 6th week of radiation therapy to 5 years post radiation therapy.
Prognostic value of genomic and proteomic markers for the primary and secondary clinical endpoints
time frame: Date of randomization to timepoint of the respective primary or secondary endpoint.
Assessment of the relationship(s) between the American Urological Association Symptom Index (AUA SI) and urinary morbidity (Adverse Event terms: Urinary frequency/urgency) using the CTCAE v. 3.0 grading system
time frame: From the 6th week of radiation therapy to 5 years post radiation therapy.

Eligibility Criteria

Male participants at least 18 years old.

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/mm^3 - 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

Additional Information

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
Principal investigator Alan Pollack, MD, PhD
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.