NCT02793765

Docetaxel Followed by Provenge in Metastatic Prostate Cancer

Docetaxel Followed by Provenge in Castration-Resistant Prostate Cancer

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: The University of Texas Health Science Center, Houston · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This clinical study will evaluate the role of combination therapy of docetaxel followed by Provenge for patients with metastatic castration-resistant prostate cancer (CRPC, (prostate cancer that is resistant to medical or surgical treatments that lower testosterone). The purpose of this study is to look at the combination therapy of docetaxel followed by Provenge to correlate the immunological biomarkers with clinical results for therapy. Biomarkers are genes, proteins and other molecules that affect how cancer cells grow, multiply, die and respond to other compounds in the body. The study drugs are approved by the Food and Drug Administration (FDA). Treatment will be administered on an outpatient basis. Patients will receive 6 cycles of docetaxel followed by Provenge. Docetaxel is an antineoplastic (chemotherapy that affects cancer cell growth) agent. Docetaxel dose of 75 mg/m2 will be given intravenously as a 1-hour infusion every 21 days on Day 1 for 6 cycles. Provenge is an immunotherapy (vaccine made from patient's own blood cells) that reprograms immune cells to attack cancer. A course of therapy consists of three doses of Provenge administered at 2-week intervals. The strategy aims to determine whether cytokine production and T cell infiltration of tumor cells could favor regression using a combination of chemotherapy plus vaccine. Tissue endpoints will include biopsies prior to first chemotherapy and first vaccine therapy and at the end of each therapy. Prostate cancer tissue infiltrates will be studied for expression of CD3, CD4, CD8, CD25/FOX3P, CD56, CTLA-4, PD-1, and Ki67. Additional immunological endpoints will be secondary antigen spread and various cytokine biomarkers.

Detailed description

Castration-resistant prostate cancer (CRPC) develops serial treatment resistance and is considered incurable. It is a largely indolent disease, which would give the body time to mount an effective immune response. CRPC is therefore potentially well suited for vaccine therapy. Docetaxel is an antineoplastic agent belonging to the taxoid family. The FDA-approved course of therapy for prostate cancer consists of 75 mg/m2 docetaxel given intravenously as a 1-hour infusion every 21 days on Day 1. Sipuleucel-T (Provenge), is an FDA-approved cancer vaccine therapy manufactured by culturing an individual's own freshly isolated peripheral blood mononuclear cells (PBMCs), including antigen-presenting cells (APCs) and T cells, with a fusion protein (PA-2024) composed of prostatic acid phosphatase (PAP) linked to granulocyte macrophage-colony stimulating factor (GM-CSF). A course of therapy consists of three doses of Provenge administered at 2-week intervals. This is an open-label phase II study in taxane-naïve patients with metastatic CRPC of docetaxel followed by Provenge. Adult (age \>18 years) men with metastatic CRPC. pathologically-confirmed adenocarcinoma of the prostate with clinical or radiologic evidence of metastatic disease that has progressed despite treatment with anti-androgens, inhibitors of adrenal-produced androgens (abiraterone), or androgen receptor inhibitors (enzalutamide), and who, prior to study entry are candidates to receive Standard of Care chemotherapy (e.g., docetaxel/prednisone) or immunotherapy (Provenge), will be enrolled in this study. This study will recruit a total of 32 patients with metastatic CRPC. Patients will receive 6 cycles of docetaxel followed by Provenge. Treatment will be administered on an outpatient basis. Patients must meet one of the following prognostic criteria: * PSA doubling time ≤6 months * \>10 bone lesions (only if they meet PSA doubling time criteria) * Visceral metastases * Bone and lymph node lesions The primary objective of this study is to characterize the immunological biomarkers during therapy and correlate the immunological biomarkers with clinical outcome. The strategy aims to determine whether cytokine production and T cell infiltration of tumor cells could favor regression using a combination of chemotherapy plus vaccine. Tissue endpoints will include biopsies prior to chemotherapy, on day 14 during the rest period between therapies and after vaccine therapy. Prostate cancer tissue infiltrates will be studied for expression of CD3, CD4, CD8, CD25/FOX3P, CD56, CTLA-4, PD-1, and Ki67. Additional immunological endpoints will be secondary antigen spread and various cytokine biomarkers.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
DRUG	Docetaxel
BIOLOGICAL	Sipuleucel-T

Timeline

• Start date: 2016-12-01
• Primary completion: 2018-07-01
• Completion: 2021-07-01
• First posted: 2016-06-08
• Last updated: 2017-10-30

Locations

1 site across 1 country: United States