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

Primary Purpose

Metastatic Castrate-resistant Prostate Cancer, mCRPC

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sipuleucel-T
Stereotactic Ablative Body Radiation
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Castrate-resistant Prostate Cancer

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Texas Southwestern Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

arm one

Arm Description

Sipuleucel-T and Stereotactic Ablative Body Radiation (SABR)

Outcomes

Primary Outcome Measures

Time to Progression
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

Immune Response
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.
Overall Survival (OS)
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)
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)
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.
Prostate Cancer-specific Survival (PCaSS)
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 Events
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 Life
To evaluate the cost effectiveness and health-related quality adjusted life of the combination treatment of SABR and sipuleucel T in patients with mCRPC.

Full Information

First Posted
March 6, 2013
Last Updated
April 11, 2022
Sponsor
University of Texas Southwestern Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01818986
Brief Title
Sipuleucel-T and Stereotactic Ablative Body Radiation (SABR) for Metastatic Castrate-resistant Prostate Cancer (mCRPC)
Official Title
Phase II Trial of Sipuleucel-T and Stereotactic Ablative Body Radiation (SABR) for Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
July 10, 2013 (Actual)
Primary Completion Date
December 20, 2019 (Actual)
Study Completion Date
May 25, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Castrate-resistant Prostate Cancer, mCRPC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
arm one
Arm Type
Experimental
Arm Description
Sipuleucel-T and Stereotactic Ablative Body Radiation (SABR)
Intervention Type
Drug
Intervention Name(s)
Sipuleucel-T
Other Intervention Name(s)
Provenge
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Ablative Body Radiation
Other Intervention Name(s)
SABR
Primary Outcome Measure Information:
Title
Time to Progression
Description
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/.
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Immune Response
Description
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.
Time Frame
6 week
Title
Overall Survival (OS)
Description
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.
Time Frame
60 months
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
4 years
Title
Biochemical Progression Free Survival (bPFS)
Description
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.
Time Frame
4 years
Title
Prostate Cancer-specific Survival (PCaSS)
Description
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
Time Frame
4 years
Title
Adverse Events
Description
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
Time Frame
60 months
Title
Cost Effectiveness and Health-related Quality Adjusted Life
Description
To evaluate the cost effectiveness and health-related quality adjusted life of the combination treatment of SABR and sipuleucel T in patients with mCRPC.
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Biopsy proven prostate cancer 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 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. PSA ≥ 5 ng/ml Asymptomatic or minimally symptomatic patients1. Visual Analog Scale (VAS) ≤ 4;vNo narcotic use in the last 21 days Adequate hematologic, renal, and liver function Previous treatment with surgery, radiation or hormonal therapy is allowed. Performance status ECOG 0 or 1. Life expectancy of at least 6 months Negative serology tests for human immunodeficiency virus (HIV) 1 and 2, human T cell lymphotropic virus (HTLV)-1, Hepatitis B and C. Age ≥ 18 years. Ability to understand and the willingness to sign a written informed consent Exclusion Criteria: Subjects must not have had more than two different regiments of chemotherapy previously or any chemotherapy within the past three months. Subjects may not be receiving any other investigational agents for the treatment of prostate cancer. 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. Subjects with malignant pleural effusions and malignant ascites Systemic corticosteroid use within past 28 days. Use of inhaled, intranasal, and topical steroids is acceptable. Systemic immunosuppressive therapy in the past 28 days. 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). Inability to tolerate contrast dye for baseline CT imaging. Initiation or discontinuation of biphosphonate use within past 28 days. Subjects with pathologic long-bone fractures Subjects with spinal cord compression Paget's disease of bone. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raquibul Hannan, MD, PhD
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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