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Sipuleucel-T and Stereotactic Ablative Body Radiation (SABR) for Metastatic Castrate-resistant Prostate Cancer (mCRPC)

Phase 2
Completed
Conditions
Metastatic Castrate-resistant Prostate Cancer
mCRPC
Interventions
Radiation: Stereotactic Ablative Body Radiation
Registration Number
NCT01818986
Lead Sponsor
University of Texas Southwestern Medical Center
Brief Summary

In this i-SABR (immunotherapy + Stereotactic Ablative Body Radiation) trial, the stereotactic radiation to multiple metastatic sites is delivered not only to eradicate sites of bulky progressive disease, but also to provide antigen presentation and immune stimulation which is expected to act synergistically to the concurrently administered immunotherapy Sipuleucel-T and thereby significantly improve the treatment outcome for metastatic castrate resistant prostate cancer patients (mCRPC). Both Sipuleucel-T and SABR are FDA approved therapeutic cancer treatment

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria
  1. Biopsy proven prostate cancer
  2. Patient must currently be on androgen deprivation or anti-androgen therapy with castrate levels of testosterone (< 50ng/dl). Medical castration should continue until disease progression
  3. Radiographic evidence of metastatic disease documented with bone scan or CT scan. Patients with any number of metastatic site are allowed to enroll. However, only up to six sites will be selected for SBRT treatment, at the discretion of the treating radiation oncologist.
  4. PSA ≥ 5 ng/ml
  5. Asymptomatic or minimally symptomatic patients1. Visual Analog Scale (VAS) ≤ 4;vNo narcotic use in the last 21 days
  6. Adequate hematologic, renal, and liver function
  7. Previous treatment with surgery, radiation or hormonal therapy is allowed.
  8. Performance status ECOG 0 or 1.
  9. Life expectancy of at least 6 months
  10. Negative serology tests for human immunodeficiency virus (HIV) 1 and 2, human T cell lymphotropic virus (HTLV)-1, Hepatitis B and C.
  11. Age ≥ 18 years.
  12. Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria
  1. Subjects must not have had more than two different regiments of chemotherapy previously or any chemotherapy within the past three months.
  2. Subjects may not be receiving any other investigational agents for the treatment of prostate cancer.
  3. Subjects with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  4. Subjects with malignant pleural effusions and malignant ascites
  5. Systemic corticosteroid use within past 28 days. Use of inhaled, intranasal, and topical steroids is acceptable.
  6. Systemic immunosuppressive therapy in the past 28 days.
  7. Use of any of the following within the past 28 days: Megestrol acetate (Megace®), diethyl stilbestrol (DES), or cyproterone acetate, Ketoconazole, high dose calcitriol [1,25(OH)2VitD] (i.e., > 7.0 μg/week).
  8. Inability to tolerate contrast dye for baseline CT imaging.
  9. Initiation or discontinuation of biphosphonate use within past 28 days.
  10. Subjects with pathologic long-bone fractures
  11. Subjects with spinal cord compression
  12. Paget's disease of bone.
  13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
arm oneStereotactic Ablative Body RadiationSipuleucel-T and Stereotactic Ablative Body Radiation (SABR)
arm oneSipuleucel-TSipuleucel-T and Stereotactic Ablative Body Radiation (SABR)
Primary Outcome Measures
NameTimeMethod
Time to Progression4 years

To evaluate the improvement in the time to progression (TTP) of metastatic prostate cancer after the combined treatment with sipuleucel-T and SABR to metastatic sites, as compared to the historically reported data with the treatment of sipuleucel-T alone. Progression will be evaluated in this study using the modified new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Committee \[JNCI 92(3):205-216, 2000\] with modifications suggested by PCWG2 \[49\] recommendations and as used in the Phase III clinical trial by Kantoff et. al.\[10\]. Changes in only the largest diameter (one-dimensional measurement) of the tumor lesions are used in the RECIST v1.1 criteria as outlined in http://www.recist.com/.

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)60 months

To evaluate the improvement in the overall survival (OS) of mCRPCa patients after the combined treatment with sipuleucel-T and SABR to metastatic sites, as compared to the historically reported data with the treatment of sipuleucel-T alone. Overall survival (OS) was defined as the duration of time from the start of treatment to the time of death from any cause.

Progression Free Survival (PFS)4 years

To evaluate the improvement in the progression free survival (PFS) of mCRPCa patients after the combined treatment with sipuleucel-T and SABR to metastatic sites, as compared to the historically reported data with the treatment of sipuleucel-T alone. Progression free survival (PFS) was defined as the length of time from the start of treatment to disease progression or death from any cause.

Biochemical Progression Free Survival (bPFS)4 years

To evaluate the improvement in the biochemical progression free survival (bPFS) of mCRPCa patients after the combined treatment with sipuleucel-T and SABR to metastatic sites, as compared to the historically reported data with the treatment of sipuleucel-T alone. Biochemical progression free survival was defined as the time from the beginning of treatment to PSA (prostate-specific antigen) disease progression. Biochemical progression was defined as an increase in PSA of \> 2 ng/ml from baseline and an increase of \> 25% from the baseline value and confirmed by a second measurement more than three weeks later.

Immune Response6 week

To evaluate the percentage of participants with Immune response at 6 weeks. Immune response will be measured using ELISpot assay (with PA2024). An immune endpoint will be reached by the patient if a \>100% increase in immune response is measured by ANY of the assays.

Prostate Cancer-specific Survival (PCaSS)4 years

To evaluate the improvement in the prostate cancer-specific survival (PCaSS) of mCRPCa patients after the combined treatment with sipuleucel-T and SABR to metastatic sites, as compared to the historically reported data with the treatment of sipuleucel-T alone. Prostate cancer-specific survival was defined as the percentage of patients who had not died from prostate cancer at the time of analysis

Adverse Events60 months

To evaluate the adverse events for the first 6 months after completion of radiation therapy associated with Sipuleucel-T when administered in combination with SABR to metastatic sites, as compared to the historically reported data with the treatment of Sipuleucel-T alone. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0. Adverse events not specifically defined in the NCI CTCAE will be scored on the Adverse Event log according to the general guidelines provided by the NCI CTCAE and as outlined:

Grade 1: Mild Grade 2: Moderate Grade 3: Severe or medically significant but not immediately life threatening Grade 4: Life threatening consequences Grade 5: Death related to the adverse event

Cost Effectiveness and Health-related Quality Adjusted Life4 years

To evaluate the cost effectiveness and health-related quality adjusted life of the combination treatment of SABR and sipuleucel T in patients with mCRPC.

Trial Locations

Locations (1)

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

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