Back to resultsSamarium 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
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Radiotherapy
Samarium 153
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, stage IV prostate cancer
Eligibility Criteria
DISEASE CHARACTERISTICS:
Inclusion criteria:
Histologically proven diagnosis of prostate cancer progressing after prior radical prostatectomy as indicated by one of the following:
- Postoperative prostate-specific antigen (PSA) rising above 1.0 ng/mL
- Postoperative PSA rising above 0.2 ng/mL with a surgical tumor Gleason score of 9 or 10
- Postoperative PSA rising above 0.2 ng/ml with nodal disease
- Stage II-IV disease (T2 -T4, N0-N1)
No distant metastases based on the following minimum diagnostic work up:
- History or physical examination within the past 8 weeks
- Bone scan negative for bone metastases within the past 4 months
- Abdominal imaging negative for metastases within the past 6 months
Exclusion criteria:
- Biopsy evidence of M1 disease
- Presence of neuroendocrine features in any prostate cancer specimen
PATIENT CHARACTERISTICS:
Inclusion criteria:
- Zubrod Performance Status 0-1
- Absolute neutrophil count (ANC) ≥ 1,800 cells/mm³
- Platelet count ≥ 100,000 cells/mm³
- Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is permitted)
Exclusion criteria:
- Prior invasive malignancy (except nonmelanoma skin cancer) unless disease free for a minimum of 3 years
Severe, active comorbidity, defined as follows:
- 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
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (laboratory tests for liver function and coagulation parameters, however, are not required for entry into this protocol)
- Renal failure (laboratory tests for renal function, however, are not required for entry into this protocol)
- AIDS based upon current Centers for Disease Control (CDC) definition (HIV testing is not required)
PRIOR CONCURRENT THERAPY:
No prior systemic chemotherapy for the study cancer
- Prior chemotherapy for a different cancer is permitted
- No hormonal therapy initiated within the last 3 months
- No prior radiotherapy to the pelvic region that would result in overlap of radiotherapy fields
Sites / Locations
- Arizona Oncology Services Foundation
- Auburn Radiation Oncology
- Radiation Oncology Centers - Cameron Park
- Mercy Cancer Center at Mercy San Juan Medical Center
- Kaiser Permanente Medical Center - Los Angeles
- Radiation Oncology Center - Roseville
- Radiological Associates of Sacramento Medical Group, Incorporated
- University of California Davis Cancer Center
- Mercy General Hospital
- Solano Radiation Oncology Center
- CCOP - Christiana Care Health Services
- University of Florida Shands Cancer Center
- John B. Amos Cancer Center
- Tulane Cancer Center Office of Clinical Research
- Hudner Oncology Center at Saint Anne's Hospital - Fall River
- West Michigan Cancer Center
- Regional Cancer Center at Singing River Hospital
- Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
- David C. Pratt Cancer Center at St. John's Mercy
- Billings Clinic - Downtown
- Stony Brook University Cancer Center
- McDowell Cancer Center at Akron General Medical Center
- Summa Center for Cancer Care at Akron City Hospital
- Barberton Citizens Hospital
- Robinson Radiation Oncology
- Oklahoma University Cancer Institute
- Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
- Sentara Cancer Institute at Sentara Norfolk General Hospital
- Coastal Cancer Center at Sentara Virginia Beach General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Radiotherapy + Samarium 153
Arm Description
Samarium 153 infusion followed by radiotherapy 12 weeks later
Outcomes
Primary Outcome Measures
Proportion of Patients With PSA Response (pt) Within 12 Weeks of Samarium 153 Administration
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
Completion of 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.
Number of Patients With Hematologic Toxicity at 12 Weeks
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)
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.
Acute and Late Radiotherapy-Related Adverse Events
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.
Freedom From Progression (FFP) Rate at 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.
Full Information
NCT ID
NCT00551525
First Posted
October 30, 2007
Last Updated
June 26, 2017
Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI), NRG Oncology
1. Study Identification
Unique Protocol Identification Number
NCT00551525
Brief Title
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
Official Title
A Phase II Trial of Samarium 153 Followed by Salvage Prostatic Fossa 3D-CRT or IMRT Irradiation in High-Risk, Clinically Non-Metastatic Prostate Cancer After Radical Prostatectomy
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
December 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radiation Therapy Oncology Group
Collaborators
National Cancer Institute (NCI), NRG Oncology
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, stage IV prostate cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
67 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Radiotherapy + Samarium 153
Arm Type
Experimental
Arm Description
Samarium 153 infusion followed by radiotherapy 12 weeks later
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Other Intervention Name(s)
3D-CRT, IMRT, Intensity-modulated radiation therapy
Intervention Description
3D-CRT or IMRT 64.8-70.2 Gy to the prostatic fossa begins 12 weeks (+/- 1 week) after Samarium 153 administration. Daily tumor doses of 1.8 - 2.0 Gy per day, 5 days per week x 7-8 weeks.
Intervention Type
Drug
Intervention Name(s)
Samarium 153
Other Intervention Name(s)
Samarium sm 153 lexidronam pentasodium, Quadramet
Intervention Description
Samarium 153 lexidronam dose 2.0 mCi/kg by IV injection one time within 2 weeks (+/- 3days) after registration.
Primary Outcome Measure Information:
Title
Proportion of Patients With PSA Response (pt) Within 12 Weeks of Samarium 153 Administration
Description
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.
Time Frame
Twelve weeks from the date of Samarium 153 infusion.
Secondary Outcome Measure Information:
Title
Completion of Therapy
Description
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.
Time Frame
90 days from the end of radiation therapy.
Title
Number of Patients With Hematologic Toxicity at 12 Weeks
Description
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.
Time Frame
Twelve weeks from the date of Samarium 153 infusion.
Title
Samarium 153-related Adverse Events at 12 Weeks (Percentage of Patients)
Description
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.
Time Frame
Twelve weeks from the date of Samarium 153 infusion
Title
Acute and Late Radiotherapy-Related Adverse Events
Description
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.
Time Frame
90 days from start of radiotherapy
Title
Freedom From Progression (FFP) Rate at 2 Years
Description
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.
Time Frame
From randomization to 2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Inclusion criteria:
Histologically proven diagnosis of prostate cancer progressing after prior radical prostatectomy as indicated by one of the following:
Postoperative prostate-specific antigen (PSA) rising above 1.0 ng/mL
Postoperative PSA rising above 0.2 ng/mL with a surgical tumor Gleason score of 9 or 10
Postoperative PSA rising above 0.2 ng/ml with nodal disease
Stage II-IV disease (T2 -T4, N0-N1)
No distant metastases based on the following minimum diagnostic work up:
History or physical examination within the past 8 weeks
Bone scan negative for bone metastases within the past 4 months
Abdominal imaging negative for metastases within the past 6 months
Exclusion criteria:
Biopsy evidence of M1 disease
Presence of neuroendocrine features in any prostate cancer specimen
PATIENT CHARACTERISTICS:
Inclusion criteria:
Zubrod Performance Status 0-1
Absolute neutrophil count (ANC) ≥ 1,800 cells/mm³
Platelet count ≥ 100,000 cells/mm³
Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is permitted)
Exclusion criteria:
Prior invasive malignancy (except nonmelanoma skin cancer) unless disease free for a minimum of 3 years
Severe, active comorbidity, defined as follows:
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
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects (laboratory tests for liver function and coagulation parameters, however, are not required for entry into this protocol)
Renal failure (laboratory tests for renal function, however, are not required for entry into this protocol)
AIDS based upon current Centers for Disease Control (CDC) definition (HIV testing is not required)
PRIOR CONCURRENT THERAPY:
No prior systemic chemotherapy for the study cancer
Prior chemotherapy for a different cancer is permitted
No hormonal therapy initiated within the last 3 months
No prior radiotherapy to the pelvic region that would result in overlap of radiotherapy fields
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard K. Valicenti, MD
Organizational Affiliation
Sidney Kimmel Cancer Center at Thomas Jefferson University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Oliver Sartor, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Arizona Oncology Services Foundation
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
Auburn Radiation Oncology
City
Auburn
State/Province
California
ZIP/Postal Code
95603
Country
United States
Facility Name
Radiation Oncology Centers - Cameron Park
City
Cameron Park
State/Province
California
ZIP/Postal Code
95682
Country
United States
Facility Name
Mercy Cancer Center at Mercy San Juan Medical Center
City
Carmichael
State/Province
California
ZIP/Postal Code
95608
Country
United States
Facility Name
Kaiser Permanente Medical Center - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Radiation Oncology Center - Roseville
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Radiological Associates of Sacramento Medical Group, Incorporated
City
Sacramento
State/Province
California
ZIP/Postal Code
95815
Country
United States
Facility Name
University of California Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Mercy General Hospital
City
Sacramento
State/Province
California
ZIP/Postal Code
95819
Country
United States
Facility Name
Solano Radiation Oncology Center
City
Vacaville
State/Province
California
ZIP/Postal Code
95687
Country
United States
Facility Name
CCOP - Christiana Care Health Services
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
University of Florida Shands Cancer Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0232
Country
United States
Facility Name
John B. Amos Cancer Center
City
Columbus
State/Province
Georgia
ZIP/Postal Code
31904
Country
United States
Facility Name
Tulane Cancer Center Office of Clinical Research
City
Alexandria
State/Province
Louisiana
ZIP/Postal Code
71315-3198
Country
United States
Facility Name
Hudner Oncology Center at Saint Anne's Hospital - Fall River
City
Fall River
State/Province
Massachusetts
ZIP/Postal Code
02721
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007-3731
Country
United States
Facility Name
Regional Cancer Center at Singing River Hospital
City
Pascagoula
State/Province
Mississippi
ZIP/Postal Code
39581
Country
United States
Facility Name
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
David C. Pratt Cancer Center at St. John's Mercy
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Billings Clinic - Downtown
City
Billings
State/Province
Montana
ZIP/Postal Code
59107-7000
Country
United States
Facility Name
Stony Brook University Cancer Center
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794-9446
Country
United States
Facility Name
McDowell Cancer Center at Akron General Medical Center
City
Akron
State/Province
Ohio
ZIP/Postal Code
44307
Country
United States
Facility Name
Summa Center for Cancer Care at Akron City Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44309-2090
Country
United States
Facility Name
Barberton Citizens Hospital
City
Barberton
State/Province
Ohio
ZIP/Postal Code
44203
Country
United States
Facility Name
Robinson Radiation Oncology
City
Ravenna
State/Province
Ohio
ZIP/Postal Code
44266
Country
United States
Facility Name
Oklahoma University Cancer Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107-5541
Country
United States
Facility Name
Sentara Cancer Institute at Sentara Norfolk General Hospital
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Coastal Cancer Center at Sentara Virginia Beach General Hospital
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23454
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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