Title 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
IRB RTOG 0534
Hospital Fairview, Hillcrest, Independence, Main Campus, North Coast Cancer, Strongsville, Wooster
Phase Phase 3
- To determine whether the addition of NC-STAD to PBRT improves freedom from progression (FFP) [maintenance of a 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 RT after radical prostatectomy
- To determine whether NC-STAD+PLNRT+PBRT improves FFP over that of NC-STAD+PBRT and PBRT alone in men treated with salvage RT 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 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; it is hypothesized that QOL as measured by the EPIC will significantly worsen by the increasing aggressiveness of treatment and that cognition as measured by the neurocognitive test battery (the HVLT-R, Trail Making Test, parts A & B, and the COWAT) will be significantly worse in the arms with NC-STAD
- To assess whether mood is improved and depression is decreased with the more aggressive therapy if it improves FFP; it is hypothesized that QOL as measured by the HSCL-25 will significantly improve with the increasing aggressiveness of treatment due to improved FFP
- An exploratory aim is to assess whether an incremental gain in FFP and survival with more aggressive therapy outweighs decrements in the primary generic domains of health related quality of life (i.e., mobility, self care, usual activities, pain/discomfort, and anxiety/depression). This aim is reported as the Quality Adjusted FFP Year (QAFFPY) and as the Quality Adjusted Life Year (QALY). The QAFFPY and QALY will be compared among treatment arms and to the literature as described in Section 1.6.
- An exploratory aim is 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. Cost-utility will be assessed by the EQ-5D among treatment arms to determine which therapy dominates.
- An exploratory aim is to assess associations between serum levels of beta-amyloid (Abeta) and measures of cognition (as measured by the HVLT-R, Trail Making Tests, parts A & B, or the COWAT) and mood and depression (as measured by the HSCL-25)
- To collect paraffin-embedded tissue blocks, serum, plasma, urine, and whole blood for future translational research analyses
- 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.
- 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, including retropubic, perineal, laparoscopic or robotically assisted. 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. There is no time limit for the date of radical prostatectomy.
- A 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 with or without a positive prostatectomy surgical margin; or
- T2N0/Nx disease with or without a positive prostatectomy surgical margin;
- Prostatectomy Gleason score of 9 or less;
- Zubrod Performance Status of 0-1;
- Age ≥ 18;
- No distant metastases, based upon the following minimum diagnostic workup:
- History/physical examination (including digital rectal exam) within 8 weeks (60 days) prior to registration;
- A CT scan of the pelvis (with contrast if renal function is acceptable; a noncontrast CT is permitted if the patient is not a candidate for contrast) or MRI of the pelvis within 120 days prior to registration;
- Bone scan within 120 days prior to registration; if the bone scan is suspicious, a plain x-ray and/or MRI must be obtained to rule out metastasis.
- Adequate bone marrow function, within 90 days prior to registration, defined as follows:
- Platelets ≥ 100,000 cells/mm3 based upon CBC;
- Hemoglobin ≥ 10.0 g/dl based upon CBC (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is recommended).
- AST or ALT < 2 x the upper limit of normal within 90 days prior to registration;
- Serum total testosterone must be ≥ 40% of the lower limit of normal (LLN) of the assay used (testosterone divided by LLN must be ≥ 0.40) within 90 days prior to registration (Note: Patients who have had a unilateral orchiectomy are eligible as long as this requirement is met)
- Patients must sign a study-specific informed consent prior to study entry.
- A palpable prostatic fossa abnormality/mass suggestive of recurrence, unless shown by biopsy under ultrasound guidance not to contain cancer;
- 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;
- Androgen deprivation therapy started prior to prostatectomy for >l; 6 months (180 days) duration. Note: The use of finasteride or dutasteride (+ or - tamsulosin) for longer periods prior to prostatectomy is acceptable;
- Androgen deprivation therapy started after prostatectomy and prior to registration (Note: The use of finasteride or dutasteride (+ PR - tamsulosin) after prostatectomy is not acceptable - must be stopped within 3 months after prostatectomy. Androgen deprivation therapy must be stopped within 3 months after prostatectomy);
- Neoadjuvant chemotherapy before or after prostatectomy;
- Prior chemotherapy for any other disease site if given within 5 years prior to registration;
- Prior cryosurgery or brachytherapy of the prostate; prostatectomy should be the primary treatment and not a salvage procedure;
- Prior pelvic radiotherapy;
- Prior invasive malignancy (except non-melanomatous skin cancer) or superficial bladder cancer unless disease free for a minimum of 5 years (for example, carcinoma in situ of the oral cavity is permissible);
- Severe, active co-morbidity, defined as follows:
- History of inflammatory bowel disease;
- History of hepatitis B or C; Blood tests are not required to determine if the patient has had hepatitis B or C, unless the patient reports a history of hepatitis.
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
- Transmural myocardial infarction within the last 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; AST or ALT are required (see Section 3.1.9); note, however, that laboratory tests for coagulation parameters are not required for entry into this protocol.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; Note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may result in increased toxicity and immunosuppression.
- Prior allergic reaction to the study drug(s) involved in this protocol.