Conditions: Prostate Cancer Prostate Neoplasms Neoplasms, Prostatic
Keywords: PSA Vaccine Immunotherapy Immune Response Androgen Deprivation Therapy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 74
Healthy volunteers: no

Brief summary:
Background:

Metastatic castrate-sensitive prostate cancer is cancer that has spread beyond the prostate area. It can be controlled by lowering the amount of testosterone in the body. This is called androgen deprivation therapy (ADT). The vaccine PROSTVAC might help the immune system kill cancer cells. Researchers want to add PROSTVAC and docetaxel chemotherapy to ADT. They think this may work better against prostate cancer than ADT alone.

Objective:

To test if adding PROSTVAC and docetaxel to ADT works better against prostate cancer than ADT alone.

Eligibility:

Men ages 18 years and over with metastatic castrate-sensitive prostate cancer

Design:

Participants will be screened with:

Physical exam

Medical history

Blood tests

Possible computed tomography (CT), magnetic resonance imaging (MRI), or bone scan: Participants lie in a machine. The machine takes pictures of the body.

Electrocardiogram: Soft electrodes are stuck to the skin to record heart signals.

Participants will have 2 optional tumor biopsies during the study.

Participants will join 1 of 2 groups. Both groups will get:

ADT

Docetaxel by vein

Steroids by mouth or vein before each docetaxel infusion

PROSTVAC injection

Both groups first have ADT. One to 4 months after, they have:

Group A:

Docetaxel every 3 weeks for 6 cycles

PROSTVAC 3 weeks after the last infusion

Booster injections 2 weeks later and then every 3 weeks, for 6 boosters total

Group B:

PROSTVAC

Booster 2 weeks later

Docetaxel hours later

Docetaxel and the booster every 3 weeks for 6 cycles

Participants will have a visit 4-5 weeks after the last treatment. They will then have visits every 12 weeks.

Participants will be followed for up to 15 years. This includes physical exams every year for 5 years.

Detailed description:
Background:

* A phase III trial demonstrated that combining docetaxel and androgen deprivation therapy (ADT) significantly improved survival (57.6 vs 44.0 months (hazard ration (HR)=0.56, (0.44-0.70), p \<0.0001) for men with metastatic castration sensitive prostate cancer (mCSPC).
* PROSTVAC (developed by the National Cancer Institute \[NCI\] and licensed to Bavarian Nordic Immunotherapeutics, Mountain View, California (CA) is a therapeutic cancer vaccine for prostate cancer.
* Preclinical and clinical studies support the potential synergy in the combination of docetaxel and PROSTVAC. The potential to combine docetaxel with vaccine in mCSPC could improve upon the survival advantage that has been previously seen.

Objectives:

Primary

-To determine if PROSTVAC combined with docetaxel is able to induce greater antigen spreading (i.e. a broader immune response) with greater associated response score compared to docetaxel alone after 19 weeks.

Key Eligibility Criteria:

* Must have castrate sensitive prostate cancer (rising PSA and testosterone over 100) or is within 134 days of starting ADT (Arm A or B) or within 28 days of start ADT (Arm C)
* Histopathological confirmation of prostate cancer
* Patients must have metastatic disease
* Patients must have a performance status of 0 to 2 according to the Eastern Cooperative Oncology Group (ECOG) criteria
* Patients must have adequate bone marrow, hepatic, and renal function

Design

* This is a randomized trial of ADT followed by simultaneous docetaxel 75 mg/m(2) every (q)3 weeks x 6 cycles + PROSTVAC q3 weeks x 6 cycles versus ADT followed by sequential docetaxel 75 mg/m(2) q3 weeks x 6 cycles followed by PROSTVAC q3 weeks x 6 cycles in men with newly diagnosed mCSPC.
* Patients who have not started ADT or who have been on ADT 28 days or fewer will be assigned to treatment with PROSTVAC for 4 - 6 injections followed by docetaxel 75 mg/m\^2 q3 weeks x 6 cycles.

Arms:
arm 1: Standard androgen deprivation therapy (ADT) followed by sequential docetaxel + prostvac arm 2: Standard androgen deprivation therapy (ADT) followed by combined docetaxel + prostvac arm 3: Standard androgen deprivation therapy (ADT) followed by prostvac, then docetaxel. No ADT for less than 28 days, prostvac prior to docetaxel.

Interventions: intervention 1: PROSTVAC-V intervention 2: PROSTVAC-F intervention 3: Docetaxel
Intervention descriptions: intervention 1: It is a recombinant vaccinia virus vector vaccine containing the genes for human prostate-specific antigen (PSA) and three co-stimulatory molecules (cluster of differentiation 80 (B7.1), intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 3 (LFA-3). It will be given subcutaneously, 2x10(8) infectious units. intervention 2: It is a recombinant fowlpox virus vector vaccine containing the genes for human prostate-specific antigen (PSA) and three co-stimulatory molecules (cluster of differentiation 80 (B7.1), intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function-associated antigen 3 (LFA-3). It will be given subcutaneously, 1x10(9) infectious units. intervention 3: It is commercially available. It will be administered at 75 mg/m(2) intravenously.

Protocol document:
Prot_SAP_000.pdf: 
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