Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer

Phase 2

Completed

Conditions: Prostate Cancer
Prostate Neoplasms
Neoplasms, Prostatic

Interventions: Biological: PROSTVAC-V
Biological: PROSTVAC-F
Drug: Docetaxel

Registration Number: NCT02649855

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 74

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C/ PROSTVAC Prior to Docetaxel	PROSTVAC-F	Standard androgen deprivation therapy (ADT) followed by prostvac, then docetaxel. No ADT for less than 28 days, prostvac prior to docetaxel.
Arm A/Sequential Docetaxel followed by PROSTVAC	PROSTVAC-V	Standard androgen deprivation therapy (ADT) followed by sequential docetaxel + prostvac
Arm A/Sequential Docetaxel followed by PROSTVAC	PROSTVAC-F	Standard androgen deprivation therapy (ADT) followed by sequential docetaxel + prostvac
Arm B/ Combined Docetaxel with PROSTVAC	PROSTVAC-V	Standard androgen deprivation therapy (ADT) followed by combined docetaxel + prostvac
Arm B/ Combined Docetaxel with PROSTVAC	PROSTVAC-F	Standard androgen deprivation therapy (ADT) followed by combined docetaxel + prostvac
Arm C/ PROSTVAC Prior to Docetaxel	PROSTVAC-V	Standard androgen deprivation therapy (ADT) followed by prostvac, then docetaxel. No ADT for less than 28 days, prostvac prior to docetaxel.
Arm A/Sequential Docetaxel followed by PROSTVAC	Docetaxel	Standard androgen deprivation therapy (ADT) followed by sequential docetaxel + prostvac
Arm B/ Combined Docetaxel with PROSTVAC	Docetaxel	Standard androgen deprivation therapy (ADT) followed by combined docetaxel + prostvac
Arm C/ PROSTVAC Prior to Docetaxel	Docetaxel	Standard androgen deprivation therapy (ADT) followed by prostvac, then docetaxel. No ADT for less than 28 days, prostvac prior to docetaxel.

Primary Outcome Measures

Name	Time	Method
Antigen Spreading (i.e., a Broader Immune Response) With Greater Associated Response Score Compared to Docetaxel Alone After 19 Weeks	After 19 Weeks	Antigen spreading as measured by antigen spread score. The antigen spreading score denotes the presence of a T-cell (cluster of differentiation(CD8)+ and/or cluster of differentiation 4(CD4+) immune response against 2 tumor associated antigens that were not targeted by PROSTVAC:Mucin 1(MUC-1) \& carcinoembryonic antigen(CEA). Antigen-specific T-cell responses were determined using intracellular cytokine staining of 4 established markers (Lysosome-associated membrane proteins h-LAMP1, interferon gamma, interleukin-2\& tumor necrosis factor) in both CD4+\& CD8+T-cells, giving a total of 8 measures of activation per antigen. Numbers of activation markers per antigen were totaled \& multiplied by 1.5 to give higher weighting to T-cell responses to antigens that were not targeted by PROSTVAC;\& the scores for both MUC-1 \& CEA were totaled per participant, with a possible range of 0-24 (0 is a negative result whereas 1.5-24 are positive results). The higher level of response, the better outcome.

Secondary Outcome Measures

Name	Time	Method
Antigen Specific T-cell Immune Composite Response Scores Between All Arms at 39 Weeks and 1 Year	39 weeks and 1 year	Response score denotes the presence of a T-cell (cluster of differentiation 8(CD8+) and/or cluster of differentiation 4(CD4+) response against 3 tumor associated antigens: prostate-specific antigen(PSA), mucin 1(MUC-1) and carcinoembryonic antigen(CEA). Antigen-specific T-cell immune responses were determined using intracellular cytokine staining of 4 established markers (Lysosome-associated membrane proteins h-LAMP1, interferon gamma, interleukin-2\& tumor necrosis factor in both CD4+ \& CD8+T-cells, a total of 8 measures of activation per antigen. The number of activation markers for PSA were totaled for a maximum score of 8. Numbers of activation markers for MUC-1 \& CEA were totaled \& multiplied by 1.5 to give higher weighting to T-cell responses to antigens that were not targeted by PROSTVAC. The scores for PSA, MUC-1 \& CEA were totaled per participant, with a possible range of 0-32 (0 is a negative result whereas 1-32 are positive results). Higher level of response, better outcome.
Number of Participants With T-cell Response to Prostate-specific Antigen (PSA)	39 weeks and 1 year	PSA-specific immune responses T-cell responses were assessed using nonparametric methods. The value denotes the number of participants with T-cell immune responses towards PSA. The higher level of response, the better outcome.