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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00551525
First Posted: October 31, 2007
Last Update Posted: July 25, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Cancer Institute (NCI)
NRG Oncology
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
  Purpose

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.


Condition Intervention Phase
Prostate Cancer Radiation: Radiotherapy Drug: Samarium 153 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Proportion of Patients With PSA Response (pt) Within 12 Weeks of Samarium 153 Administration [ Time Frame: 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:
  • Completion of Therapy [ Time Frame: 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.

  • Number of Patients With Hematologic Toxicity at 12 Weeks [ Time Frame: 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) [ Time Frame: 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.

  • Acute and Late Radiotherapy-Related Adverse Events [ Time Frame: 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.

  • Freedom From Progression (FFP) Rate at 2 Years [ Time Frame: 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.


Enrollment: 67
Study Start Date: April 2008
Study Completion Date: December 2016
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Radiotherapy + Samarium 153
Samarium 153 infusion followed by radiotherapy 12 weeks later
Radiation: Radiotherapy
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.
Other Names:
  • 3D-CRT
  • IMRT
  • Intensity-modulated radiation therapy
Drug: Samarium 153
Samarium 153 lexidronam dose 2.0 mCi/kg by IV injection one time within 2 weeks (+/- 3days) after registration.
Other Names:
  • Samarium sm 153 lexidronam pentasodium
  • Quadramet

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00551525


  Show 29 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
NRG Oncology
Investigators
Principal Investigator: Richard K. Valicenti, MD Sidney Kimmel Cancer Center at Thomas Jefferson University
Study Chair: Oliver Sartor, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00551525     History of Changes
Obsolete Identifiers: NCT01317043
Other Study ID Numbers: RTOG-0622
CDR0000570622
NCI-2009-01094 ( Registry Identifier: CTRP(Clinical Trial Reporting Program) )
First Submitted: October 30, 2007
First Posted: October 31, 2007
Results First Submitted: September 6, 2016
Results First Posted: July 25, 2017
Last Update Posted: July 25, 2017
Last Verified: June 2017

Keywords provided by Radiation Therapy Oncology Group:
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Samarium Sm-153 lexidronam
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs