Trial record 1 of 1 for:    NCT00567580
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Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer

This study is currently recruiting participants.
Verified December 2013 by Radiation Therapy Oncology Group
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00567580
First received: December 4, 2007
Last updated: December 17, 2013
Last verified: December 2013

December 4, 2007
December 17, 2013
February 2008
December 2020   (final data collection date for primary outcome 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. ] [ Designated as safety issue: No ]
Freedom from progression (FFP)
Complete list of historical versions of study NCT00567580 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • Distant metastasis [ Time Frame: From randomization to documented (by imaging) distant disease. ] [ Designated as safety issue: No ]
  • Cause-specific mortality [ Time Frame: From date of randomization to the date of death due to prostate cancer. ] [ Designated as safety issue: No ]
  • Overall mortality [ Time Frame: From the date of randomization to the date of death due to any cause. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: Yes ]
  • Secondary biochemical failure
  • Hormone-refractory disease
  • Local failure
  • Distant metastasis
  • Cause-specific mortality
  • Overall mortality
  • Incidence of acute adverse events ≤ 90 days of the completion of radiotherapy (RT)
  • Time to late grade 2+ and 3+ adverse events assessed > 90 days from the completion of RT
  • Comparison of disease-specific health related quality of life (HRQOL) change by EPIC, HVLT-R, Trail Making Test, parts A & B, and COWAT
  • Assessment of mood and depression change using QOL measured by the HSCL-25
  • Assessment and comparison of Quality Adjusted Life Year (QALY) and Quality Adjusted FFP Year (QAFFPY)
  • Evaluation and comparison of the cost-utility using EQ-5D
  • 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
  • Prognostic value of genomic and proteomic markers for the primary and secondary clinical endpoints
  • Collection of paraffin-embedded tissue blocks, serum, plasma, urine, and buffy coat cells for future translational research analyses
  • 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
Not Provided
Not Provided
 
Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • Drug: bicalutamide
    Oral, daily
  • Drug: flutamide
    Oral, daily
  • Radiation: radiation therapy
    Once daily, 5 days a week
  • Active Comparator: 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).
    Intervention: Radiation: radiation therapy
  • Experimental: 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 (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.
    Interventions:
    • Drug: bicalutamide
    • Drug: flutamide
    • Radiation: radiation therapy
  • Experimental: 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).
    Interventions:
    • Drug: bicalutamide
    • Drug: flutamide
    • Radiation: radiation therapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1764
Not Provided
December 2020   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
Not Provided
United States,   Canada,   China,   Israel
 
NCT00567580
RTOG 0534, CDR0000577574, NCI-2009-00733
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
  • National Cancer Institute (NCI)
  • Cancer and Leukemia Group B
Principal Investigator: Alan Pollack, MD, PhD Fox Chase Cancer Center
Study Chair: Leonard G. Gomella, MD Jefferson Medical College of Thomas Jefferson University
Study Chair: Joycelyn L. Speight, MD, PhD University of California, San Francisco
Radiation Therapy Oncology Group
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP