Sipuleucel-T Combined With Bipolar Androgen Therapy in Men With mCRPC

NCT ID: NCT06100705

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-20
• Study Completion Date: 2028-03-31

Brief Summary

This is an open-label, single-arm phase II study of bipolar androgen therapy (BAT) given in addition with standard of care Sipuleucel-T to determine the interferon (IFN) gamma Enzyme-linked Immunospot (ELISPOT) response rate to PA2024 (an engineered fusion protein of prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor which the activated autologous dendritic cells in the Sipuleucel-T vaccine are loaded with) in patients with metastatic castration resistant prostate cancer (mCRPC).

Detailed Description

The primary endpoint is the immune response to PA2024 as measured by ELISPOT by week 26. This immunological endpoint was chosen as the primary based on the data showing the Sipuleucel-T immune parameters correlating with overall survival from the pooled analysis phase III trials of Sipuleucel-T (Sheikh NA et al. Cancer Immunol Immunother 2013). Secondary endpoints include other immune parameters related to the Sipuleucel-T, including (1) APC cumulative activation (CD54 upregulation), (2) APC number and (3) total nucleated cells (TNC) count, which also have correlated with survival outcomes and clinical endpoints, and (4) T cell proliferation response to PA2024 and PAP, (5) ex vivo cytokine profile and (6) humoral response to PA2024 and PAP, clinical endpoints including: (7) PSA50 response rate (PSA50 RR), (8) objective response rate (ORR), (9) radiographic progression-free survival (rPFS), and (10) overall survival (OS), (11) safety and tolerability. We hypothesize that BAT potentiates the anti-tumor immune response and enhances clinical outcomes when given before and concurrently with Sipuleucel-T. Secondarily, we also hypothesize that the clinical activity of BAT will increase with concurrent Sipuleucel-T, as measured by PSA50 response rate and objective response rate compared to historical controls.

Participants will start with testosterone injection every 4 weeks. The first dose of standard of care Sipuleucel-T will be prepared and infused after two doses of testosterone and will continue every 2 weeks for a total of 3 infusions at a standard schedule. The testosterone injection will continue once every 4 weeks until treatment discontinuation criteria are met.

The participants will be assessed with HPE, and PSA every 4 weeks, and radiographic assessment per PCWG3 every 12 weeks. DEPO-Testosterone (testosterone cypionate) IM injection will continue until disease progression, unacceptable toxicity, or withdrawal of consent to treatment.

Conditions

Metastatic Castration-resistant Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Testosterone Cypionate + Sipuleucel-T

Participants will start with testosterone injection every 4 weeks. The first dose of standard of care Sipuleucel-T will be prepared and infused after two doses of testosterone and will continue every 2 weeks for a total of 3 infusions at a standard schedule. The testosterone injection will continue once every 4 weeks until treatment discontinuation criteria are met.

Group Type: EXPERIMENTAL

Testosterone Cypionate

Intervention Type: DRUG

Testosterone Cypionate is an androgen and anabolic steroid medication which is used mainly in the treatment of low testosterone levels in men.

Sipuleucel-T

Intervention Type: DRUG

Sipuleucel-T is the first FDA-approved immunotherapy in treatment of mCRPC. It is a therapeutic cancer vaccine composed of activated autologous dendritic cells loaded with an engineered fusion protein of prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor, PAP-GMCSF, also called PA2024. This cellular product is prepared in three steps: (1) leukapheresis to isolate CD54+ dendritic cells, (2) the cells and harvested and cultured with PA2024 ex vivo, and (3) re-infusion of the activated DC into the original patient. The preparation and administration of this autologous cellular product are done every 2 weeks for a total of three infusions and is designed to elicit an immune response to prostatic acid phosphatase.

Interventions

Testosterone Cypionate

Testosterone Cypionate is an androgen and anabolic steroid medication which is used mainly in the treatment of low testosterone levels in men.

Intervention Type: DRUG

Sipuleucel-T

Sipuleucel-T is the first FDA-approved immunotherapy in treatment of mCRPC. It is a therapeutic cancer vaccine composed of activated autologous dendritic cells loaded with an engineered fusion protein of prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor, PAP-GMCSF, also called PA2024. This cellular product is prepared in three steps: (1) leukapheresis to isolate CD54+ dendritic cells, (2) the cells and harvested and cultured with PA2024 ex vivo, and (3) re-infusion of the activated DC into the original patient. The preparation and administration of this autologous cellular product are done every 2 weeks for a total of three infusions and is designed to elicit an immune response to prostatic acid phosphatase.

Intervention Type: DRUG

Other Intervention Names

DEPO-Testosterone; Provenge

Eligibility Criteria

Inclusion Criteria

• Written informed consent obtained prior to the initiation of study procedures.
• Patients who meet the US FDA-approved indication for Sipuleucel-T: for asymptomatic or minimally symptomatic mCRPC at the discretion of the treating investigator.
• Histologically confirmed adenocarcinoma of the prostate.
• Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone scan and/or computed tomography (CT) scan or Magnetic Resonance Image (MRI).
• Progressive castration-resistant prostate cancer (CRCP): Participants must have current or historical evidence of disease progression concomitant with surgical or medical castration and during immediate past systemic therapy, as demonstrated by (a) PSA progression, or (b) progression of measurable disease, or (c) progression of non-measurable disease as defined below:

1. By PSA: two consecutively rising PSA values, at least 7 days apart, each ≥ 1.0 ng/mL and ≥ 50% above the minimum PSA observed during castration therapy or above the pre-treatment value if there was no response.

2. By measurable disease: Progressive disease by RECIST v1.1 criteria

3. By non-measurable disease

i. Soft tissue disease: The appearance of 1 or more new lesions, and/or unequivocal worsening of non-measurable disease when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response.

ii. Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan when compared to imaging studies acquired during castration therapy or against the pre-castration studies if there was no response. Increased uptake of pre-existing lesions on bone scan does not constitute progression.

• Castration status confirmed by serum testosterone level <50ng/dL
• ECOG Performance Status of 0 or 1.
• Adequate liver function:

1. Bilirubin <2.0 x institutional upper limit of normal (UNL)

2. AST (SGOT) <2.5 x UNL

3. ALT (SGPT) <2.5 x UNL

• Acceptable renal function

a) Serum creatinine <2.0 x UNL

• Acceptable hematologic function:

1. Absolute neutrophil count (ANC) > 1.0 x10^9 cells /L)

2. Platelet counts > 100 x 10^9 / L)

3. Hemoglobin >9 g/dL

Exclusion Criteria

• PSA >20ng/dL within the 4 weeks prior to signing ICF
• Previously treated with three or more FDA-approved androgen/AR signaling inhibitors (ASI) (e.g., abiraterone, enzalutamide, apalutamide, darolutamide). No minimum number of ASI is required.
• Prior chemotherapy for mCRPC. However, prior chemotherapy administered for mCSPC is allowed unless the disease progression to CRPC occurred within 12 months from the last dose of chemotherapy.
• Prior treatment with Sipuleucel-T or supraphysiologic dose of testosterone treatment for prostate cancer.
• Prior systemic treatment with ASI, PARP inhibitor or Radium-223 or other systemic anti-cancer therapy for prostate cancer within 4 weeks prior to start of treatment.
• Prior prednisone >10mg (or its equivalent) within 2 weeks prior to registration.
• Prior immunotherapy or Lu177 PSMA radioligand therapy within 6 weeks prior to registration.
• Prior palliative radiotherapy within 2 weeks prior to registration.
• Radiographic evidence of hepatic metastases
• Use of narcotics including tramadol or stronger for cancer-related pain within 4 weeks prior to signing ICF. Use of NSAIDs or acetaminophen is allowed.
• Active autoimmune disease requiring systemic corticosteroids of prednisone greater than 10mg a day or the equivalent dose of other corticosteroids.
• Known active HIV, Hepatitis B or Hepatitis C or Human T cell Lymphotropic virus (HTLV)-1 infection. Testing is not required. Note: Participants with resolved, historic HIV, Hepatitis B or Hepatitis C or Human T cell Lymphotropic virus (HTLV)-1 will be assessed by the PI and deemed eligible if their viral infections are in remission: without detectable viruses and secondary immunodeficiency, and without requiring any treatments that affects immune function. Eligibility will be determined after a discussion with the PI and adequate standard clinical tests are acquired to prove that they are in remission.
• Active infection requiring parenteral antibiotic therapy or causing fever (temperature >100.5 in Fahrenheit scale) within 1 week prior to registration.
• Life expectancy of less than 6 months prior to signing ICF.
• Any medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dendreon

INDUSTRY

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Joseph W Kim

Associate Professor of Internal Medicine (Medical Oncology)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph W Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale Cancer Center

New Haven, Connecticut, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Laura Kane

Role: CONTACT

Laura.Kane@yale.edu

7733696904

Facility Contacts

Joseph W Kim

Role: primary

joseph.w.kim@yale.edu

12037376467

Other Identifiers

2000035188

Identifier Type: -

Identifier Source: org_study_id