Docetaxel and PROSTVAC for Metastatic Castration-Sensitive Prostate Cancer

NCT02649855 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 16004816-C-0048
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer; Prostate Neoplasms; Neoplasms, Prostatic

Keywords

PSA; Vaccine; Immunotherapy; Immune Response; Androgen Deprivation Therapy

Outcome Measures

Primary Outcomes (1)

• Antigen Spreading (i.e., a Broader Immune Response) With Greater Associated Response Score Compared to Docetaxel Alone 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.

  After 19 Weeks

Secondary Outcomes (2)

• Antigen Specific T-cell Immune Composite Response Scores Between All Arms at 39 Weeks and 1 Year

  39 weeks and 1 year

• Number of Participants With T-cell Response to Prostate-specific Antigen (PSA)

  39 weeks and 1 year

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 70 months and 4 days for Arm A, 38 months and 28 days for Arm B, and 43 months and 29 days for Arm C.

Study Arms (3)

Arm A/Sequential Docetaxel followed by PROSTVAC

EXPERIMENTAL

Standard androgen deprivation therapy (ADT) followed by sequential docetaxel + prostvac

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

Arm B/ Combined Docetaxel with PROSTVAC

EXPERIMENTAL

Standard androgen deprivation therapy (ADT) followed by combined docetaxel + prostvac

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

Arm C/ PROSTVAC Prior to Docetaxel

EXPERIMENTAL

Standard androgen deprivation therapy (ADT) followed by prostvac, then docetaxel. No ADT for less than 28 days, prostvac prior to docetaxel.

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

Interventions

PROSTVAC-V BIOLOGICAL

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.

Arm A/Sequential Docetaxel followed by PROSTVAC; Arm B/ Combined Docetaxel with PROSTVAC; Arm C/ PROSTVAC Prior to Docetaxel

PROSTVAC-F BIOLOGICAL

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.

Arm A/Sequential Docetaxel followed by PROSTVAC; Arm B/ Combined Docetaxel with PROSTVAC; Arm C/ PROSTVAC Prior to Docetaxel

Docetaxel DRUG

It is commercially available. It will be administered at 75 mg/m(2) intravenously.

Also known as: Taxotere

Arm A/Sequential Docetaxel followed by PROSTVAC; Arm B/ Combined Docetaxel with PROSTVAC; Arm C/ PROSTVAC Prior to Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented histopathological confirmation of prostate cancer-from a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
• Patients must have metastatic disease, defined as at least one lesion on bone scan or at least one lesion that are measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Patients who have metastatic disease by these criteria prior to ADT, but then have changes after androgen deprivation therapy (ADT) that diminish the size of these lesions or changes on bone scan are still eligible.)
• 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 with:
• Absolute neutrophil count (ANC) greater than or equal to 1500/microL, without cerebrospinal fluid (CSF) support
• Platelets greater than or equal to 100,000/microL
• Aspartate aminotransferase (AST)/Serum glutamic-oxaloacetic transaminase (SGOT) less than or equal to 2.5 times upper limit of normal (ULN);
• Alanine aminotransferase (ALT)/Serum glutamic-pyruvic transaminase (SGPT) less than or equal to 2.5 times upper limit of normal (ULN);
• Total serum bilirubin less than or equal to 1.5 times upper limit of normal (ULN), OR in patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0)
• Serum albumin greater than or equal to 2.8 g/dL
• Lipase \< 2.0 times the upper limit of normal and no radiologic or clinical evidence of pancreatitis
• Creatinine less than or equal to 1.5 times institutional upper limits of normal
• Creatinine clearance of greater than or equal to 50 ml/min/1.73 m(2) for patients with creatinine levels above institutional normal by 24-hour urine.
• Willing to travel to the National Institutes of Health (NIH) for follow-up visits
• years of age or older.

You may not qualify if:

• Immunocompromised status due to:
• Human immunodeficiency virus (HIV) positivity.
• Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including central nervous system (CNS), heart, lungs, kidneys, skin, and gastrointestinal (GI) tract will be allowed.
• Other immunodeficiency diseases
• Chronic administration (defined as daily or every other day for continued use \> 14 days) of corticosteroids deemed systemic by investigator within 28 days before the first planned dose of PROSTVAC. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed.
• Evidence of rising prostate-specific antigen (PSA) on ADT
• Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with patient's ability to carry out the treatment program.
• Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to poxviral vaccines (e.g., vaccinia vaccine)
• Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).
• History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
• Previous serious adverse reactions to smallpox vaccination
• Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: (a) children less than or equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV).
• Receipt of an investigational agent within 28 days (or 60 days for an antibody-based therapy) before the first planned dose of study drugs.
• Patients who test positive for hepatitis B virus (HBV) or hepatitis C virus (HCV)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

PROSTVAC; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Dr. Melissa Abel
• Organization: National Cancer Institute

melissa.abel@mail.nih.gov

240-447-5353

Study Officials

• Melissa Abel, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 7, 2016
• First Posted: January 8, 2016
• Study Start: January 19, 2016
• Primary Completion: July 1, 2022
• Study Completion: December 5, 2023
• Last Updated: April 29, 2026
• Results First Posted: July 21, 2023

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)