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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Samarium 153

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.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Arizona Oncology Services Foundation
  • California
    • Auburn, California, United States, 95603
      • Auburn Radiation Oncology
    • Cameron Park, California, United States, 95682
      • Radiation Oncology Centers - Cameron Park
    • Carmichael, California, United States, 95608
      • Mercy Cancer Center at Mercy San Juan Medical Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Medical Center - Los Angeles
    • Roseville, California, United States, 95661
      • Radiation Oncology Center - Roseville
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Vacaville, California, United States, 95687
      • Solano Radiation Oncology Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • Florida
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center
  • Louisiana
    • Alexandria, Louisiana, United States, 71315-3198
      • Tulane Cancer Center Office of Clinical Research
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • Hudner Oncology Center at Saint Anne's Hospital - Fall River
  • Michigan
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
  • Montana
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
  • New York
    • Stony Brook, New York, United States, 11794-9446
      • Stony Brook University Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Barberton, Ohio, United States, 44203
      • Barberton Citizens Hospital
    • Ravenna, Ohio, United States, 44266
      • Robinson Radiation Oncology
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Cancer Institute at Sentara Norfolk General Hospital
    • Virginia Beach, Virginia, United States, 23454
      • Coastal Cancer Center at Sentara Virginia Beach General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 116 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Twelve weeks from the date of Samarium 153 infusion.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	90 days from the end of radiation therapy.
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.	Twelve weeks from the date of Samarium 153 infusion.
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.	Twelve weeks from the date of Samarium 153 infusion
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.	90 days from start of radiotherapy
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.	From randomization to 2 years

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Principal Investigator: Richard K. Valicenti, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• ASTRO 2015 abstract: The First Report of NRG Oncology/RTOG 0622

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: October 30, 2007
• First Submitted That Met QC Criteria: October 30, 2007
• First Posted (Estimate): October 31, 2007

Study Record Updates

• Last Update Posted (Actual): July 25, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage IV prostate cancer; stage IIB prostate cancer; stage IIA prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Samarium Sm-153 lexidronam
• Other Study ID Numbers: RTOG-0622; CDR0000570622; NCI-2009-01094 (Registry Identifier: CTRP(Clinical Trial Reporting Program))