Trial Outcomes & Findings for 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 (NCT NCT00551525)

Last Updated: 2017-07-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

67 participants

Primary outcome timeframe

Twelve weeks from the date of Samarium 153 infusion.

Results posted on

2017-07-25

Participant Flow

Participant milestones

Participant milestones
Measure	Radiotherapy + Samarium 153 Samarium 153 infusion followed by radiotherapy 12 weeks later
Overall Study STARTED	67
Overall Study COMPLETED	62
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Radiotherapy + Samarium 153 Samarium 153 infusion followed by radiotherapy 12 weeks later
Overall Study Protocol Violation	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Radiotherapy + Samarium 153 n=62 Participants Samarium 153 infusion followed by radiotherapy 12 weeks later
Age, Continuous	65 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants

PRIMARY outcome

Timeframe: Twelve weeks from the date of Samarium 153 infusion.

Population: All eligible patients who received Samarium 153 with at least 12 weeks follow-up from the injection

Outcome measures

Outcome measures
Measure	Radiotherapy + Samarium 153 n=52 Participants Samarium 153 infusion followed by radiotherapy 12 weeks later
Proportion of Patients With PSA Response (pt) Within 12 Weeks of Samarium 153 Administration	7 percentage of participants

SECONDARY outcome

Timeframe: 90 days from the end of radiation therapy.

Population: All eligible patients who started treatment and did not withdraw consent prior to 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.

Outcome measures

Outcome measures
Measure	Radiotherapy + Samarium 153 n=60 Participants Samarium 153 infusion followed by radiotherapy 12 weeks later
Completion of Therapy	93.3 percentage of participants Interval 87.0 to 99.7

SECONDARY outcome

Timeframe: Twelve weeks from the date of Samarium 153 infusion.

Population: Eligible patients who started study treatment

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.

Outcome measures

Outcome measures
Measure	Radiotherapy + Samarium 153 n=60 Participants Samarium 153 infusion followed by radiotherapy 12 weeks later
Number of Patients With Hematologic Toxicity at 12 Weeks	15 Participants

SECONDARY outcome

Timeframe: Twelve weeks from the date of Samarium 153 infusion

Population: Eligible patients with adverse event data

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.

Outcome measures

Outcome measures
Measure	Radiotherapy + Samarium 153 n=60 Participants Samarium 153 infusion followed by radiotherapy 12 weeks later
Samarium 153-related Adverse Events at 12 Weeks (Percentage of Patients)	16 percentage of participants

SECONDARY outcome

Timeframe: 90 days from start of radiotherapy

Population: Eligible patients with adverse event data

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.

Outcome measures

Outcome measures
Measure	Radiotherapy + Samarium 153 n=60 Participants Samarium 153 infusion followed by radiotherapy 12 weeks later
Acute and Late Radiotherapy-Related Adverse Events Acute	35 participants
Acute and Late Radiotherapy-Related Adverse Events Late	27 participants

SECONDARY outcome

Timeframe: From randomization to 2 years

Population: Eligible patients who started study treatment

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.

Outcome measures

Outcome measures
Measure	Radiotherapy + Samarium 153 n=60 Participants Samarium 153 infusion followed by radiotherapy 12 weeks later
Freedom From Progression (FFP) Rate at 2 Years	25.50 percentage of participants Interval 14.4 to 36.7

Adverse Events

Radiotherapy + Samarium 153

Serious events: 5 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Radiotherapy + Samarium 153 n=60 participants at risk Samarium 153 infusion followed by radiotherapy 12 weeks later
General disorders Sudden death	1.7% 1/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Leukopenia	3.3% 2/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Neutrophil count decreased	3.3% 2/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Platelet count decreased	1.7% 1/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Vascular disorders Thrombosis	1.7% 1/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.

Other adverse events

Other adverse events
Measure	Radiotherapy + Samarium 153 n=60 participants at risk Samarium 153 infusion followed by radiotherapy 12 weeks later
Blood and lymphatic system disorders Blood disorder	11.7% 7/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Blood and lymphatic system disorders Hemoglobin decreased	41.7% 25/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Gastrointestinal disorders Constipation	13.3% 8/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Gastrointestinal disorders Diarrhea	25.0% 15/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Gastrointestinal disorders Gastrointestinal disorder	15.0% 9/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Gastrointestinal disorders Hemorrhoids	6.7% 4/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Gastrointestinal disorders Nausea	10.0% 6/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Gastrointestinal disorders Proctitis	13.3% 8/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
General disorders Fatigue	50.0% 30/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
General disorders Pain [other]	5.0% 3/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Alanine aminotransferase increased	5.0% 3/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Leukopenia	65.0% 39/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Lymphopenia	18.3% 11/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Neutrophil count decreased	43.3% 26/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Investigations Platelet count decreased	76.7% 46/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Metabolism and nutrition disorders Hyperglycemia	10.0% 6/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Musculoskeletal and connective tissue disorders Pain in extremity	5.0% 3/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Nervous system disorders Dizziness	5.0% 3/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Nervous system disorders Headache	5.0% 3/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Renal and urinary disorders Urinary frequency	43.3% 26/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Renal and urinary disorders Urinary incontinence	26.7% 16/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Renal and urinary disorders Urinary retention	6.7% 4/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Renal and urinary disorders Urogenital disorder	16.7% 10/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Reproductive system and breast disorders Erectile dysfunction	11.7% 7/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Skin and subcutaneous tissue disorders Alopecia	5.0% 3/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.
Vascular disorders Hot flashes	16.7% 10/60 Subjects experiencing more than one of a given adverse event are counted only once for that adverse event. Eligible patients with any adverse event data are included.

Additional Information

Wendy Seiferheld, M.S.

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER