Samarium Sm 153 Lexidronam Pentasodium and 3-Dimensional Conformal Radiation Therapy or Intensity-Modulated Radiation Therapy in Treating Patients With Rising Prostate-Specific Antigen Levels After Radical Prostatectomy for Prostate Cancer
- Registration Number
- NCT00551525
- Lead Sponsor
- Radiation Therapy Oncology Group
- Brief Summary
RATIONALE: Giving samarium Sm 153 lexidronam pentasodium and 3-dimensional (3-D) conformal radiation therapy or intensity-modulated radiation therapy may keep prostate cancer from growing in patients with rising prostate-specific antigen (PSA) levels after radical prostatectomy for prostate cancer.
PURPOSE: This phase II trial is studying how well samarium Sm 153 lexidronam pentasodium and 3-D conformal radiation therapy or intensity-modulated radiation therapy work in treating patients with rising PSA levels after radical prostatectomy for prostate cancer.
- Detailed Description
OBJECTIVES:
Primary
* To assess the effectiveness of samarium Sm 153 lexidronam pentasodium (as determined by a 30% decline in the PSA level within 12 weeks) followed by either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy in patients with rising prostate-specific antigen levels (PSA) after radical prostatectomy prostate cancer.
Secondary
* To assess the proportion of patients completing protocol treatment.
* To evaluate hematological toxicity at 12 weeks.
* To evaluate samarium Sm 153 lexidronam pentasodium-related adverse events at 12 weeks.
* To evaluate the "acute" and "late" radiation therapy-related events having occurred up to 24 weeks from the end of radiation therapy.
* To compare the freedom from progression rate at 2 years to that predicted by the Kattan Nomograms.
OUTLINE: Patients receive samarium Sm 153 lexidronam pentasodium (SM) IV on day 1. Patients are closely monitored for prostate-specific antigen (PSA) level and SM-associated toxicity for 12 weeks. After the 12 weeks, patients undergo either intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 7-8 weeks. Patients may receive hormonal therapy (after radiation therapy) at the discretion of their physician.
Treatment continues in the absence of disease progression (defined as a PSA doubling time less than 3 months), severe thrombocytopenia (defined as a platelet count of 25,000 cells/mm³ or less), or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3 months, 6 months, and 12 months, every 6 months for 2 years, and then annually thereafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 67
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Radiotherapy + Samarium 153 Radiotherapy Samarium 153 infusion followed by radiotherapy 12 weeks later Radiotherapy + Samarium 153 Samarium 153 Samarium 153 infusion followed by radiotherapy 12 weeks later
- Primary Outcome Measures
Name Time Method Proportion of Patients With PSA Response (pt) Within 12 Weeks of Samarium 153 Administration Twelve weeks from the date of Samarium 153 infusion. A PSA response for each patient is calculated by (baseline PSA-current PSA)/baseline PSA. A decline of at least 30% is considered a response. Null hypothesis (H0): Samarium 153 is not effective (pt ≤ 0.1) vs alternative hypothesis (HA): Samarium 153 is effective (pt ≥ 0.25). The sample size of 69 analyzable patients (eligible patients receiving any protocol treatment with ≥ 12 weeks follow-up from the Samarium 153 injection) was calculated based on Fleming's Multiple Testing Procedure at a significance level of 0.019 and 91% statistical power requiring 69 patients to conclude either the null or alternative hypotheses. With only 52 analyzable patients this study had only 78% power and needed at least 11 patients with a PSA response to reject H0.
- Secondary Outcome Measures
Name Time Method Completion of Therapy 90 days from the end of radiation therapy. The completion of protocol treatment is defined as receiving at least 64.8 Gy radiation after the Samarium 153 injection. The null hypothesis that the proportion of the number of patients who complete the protocol treatment (the Samarium 153 and the radiation therapy) is less than or equal to 0.5 was tested using an exact test for a binomial proportion. If the true treatment completion proportion is 0.8, then the statistical power of a one-sided 0.378 level exact binomial test of proportion would be 94.1% with the sample size of 26. Therefore any number of analyzable patients greater than 26 patients provides enough power for this endpoint.
Acute and Late Radiotherapy-Related Adverse Events 90 days from start of radiotherapy The number of patients who experienced a grade 1-5 radiation-related adverse events within 90 days of the start of radiotherapy (acute) and after 90 days (late). Adverse events are evaluated by the NCI Common Terminology Criteria for Adverse Event (CTCAE) version 3.0. Multivariate logistic regression was used to model the association of clinical T-stage (pT2 vs. pT3 \[reference level\]), baseline PSA, Gleason score (\<8 vs. 8-10\[reference level\]), and age with the occurrence of any acute radiotherapy-related adverse event. Odds ratios and the respective 95% confidence intervals were computed for each factor. Per the protocol, late adverse events were not analyzed.
Number of Patients With Hematologic Toxicity at 12 Weeks Twelve weeks from the date of Samarium 153 infusion. Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Hematological toxicities consist of platelet grade 3-5, white blood cell grade 3-5, hemoglobin grade 3-5, and any secondary leukemia's.
Samarium 153-related Adverse Events at 12 Weeks (Percentage of Patients) Twelve weeks from the date of Samarium 153 infusion Adverse events are evaluated by the NCI Common Terminology Criteria for Adverse Event (CTCAE) version 3.0. The treatment-related attribution includes definitely, probably or possibly related to treatment. The treatment-related adverse events are:
* HEMATOLOGIC Platelet grade 3-5 White blood cell count (WBC) grade 3-5 Hemoglobin grade 3-5 Any secondary leukemia's
* HEMORRHAGE/BLEEDING Hemorrhage, gastrointestinal - anus, rectum grade 3-5 Hemorrhage, genitourinary - bladder, prostate, urethra grade 3-5
* SAMARIUM 153-RELATED GRADE 5 ADVERSE EVENT PRIOR TO TREATMENT OF RADIATION.Freedom From Progression (FFP) Rate at 2 Years From randomization to 2 years Progression is defined as biochemical (PSA) failure at any time for 2 years after prostatic fossa radiation therapy (RT), initiation of systemic therapy, or clinical failure. Biochemical failure is defined as a rise of 0.2 ng/ml or more above the nadir PSA after completion of RT followed by another higher value, or a continued rise in the serum PSA despite RT. FFP rate at 2 years was to be compared to that predicted by the Kattan Nomograms. See "Limitations and Caveats" section.
Trial Locations
- Locations (29)
Mercy Cancer Center at Mercy San Juan Medical Center
🇺🇸Carmichael, California, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Stony Brook University Cancer Center
🇺🇸Stony Brook, New York, United States
Coastal Cancer Center at Sentara Virginia Beach General Hospital
🇺🇸Virginia Beach, Virginia, United States
Solano Radiation Oncology Center
🇺🇸Vacaville, California, United States
Kaiser Permanente Medical Center - Los Angeles
🇺🇸Los Angeles, California, United States
Barberton Citizens Hospital
🇺🇸Barberton, Ohio, United States
McDowell Cancer Center at Akron General Medical Center
🇺🇸Akron, Ohio, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
Arizona Oncology Services Foundation
🇺🇸Phoenix, Arizona, United States
Oklahoma University Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Radiological Associates of Sacramento Medical Group, Incorporated
🇺🇸Sacramento, California, United States
Auburn Radiation Oncology
🇺🇸Auburn, California, United States
Radiation Oncology Centers - Cameron Park
🇺🇸Cameron Park, California, United States
Radiation Oncology Center - Roseville
🇺🇸Roseville, California, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
John B. Amos Cancer Center
🇺🇸Columbus, Georgia, United States
Regional Cancer Center at Singing River Hospital
🇺🇸Pascagoula, Mississippi, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
David C. Pratt Cancer Center at St. John's Mercy
🇺🇸Saint Louis, Missouri, United States
Robinson Radiation Oncology
🇺🇸Ravenna, Ohio, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Sentara Cancer Institute at Sentara Norfolk General Hospital
🇺🇸Norfolk, Virginia, United States
Tulane Cancer Center Office of Clinical Research
🇺🇸Alexandria, Louisiana, United States
Hudner Oncology Center at Saint Anne's Hospital - Fall River
🇺🇸Fall River, Massachusetts, United States
University of Florida Shands Cancer Center
🇺🇸Gainesville, Florida, United States
Billings Clinic - Downtown
🇺🇸Billings, Montana, United States
Mercy General Hospital
🇺🇸Sacramento, California, United States