Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer

NCT01875250 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13015313-C-0153
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Enzalutamide is a well tolerated hormone therapy that is used to treat advanced prostate cancer. It is given to help kill cancer cells and limit cancer cell growth. A new possible way of treating prostate cancer is using a therapeutic cancer vaccine (immune stimulating therapy) that may help activate the immune system against the cancer. The immune stimulating vaccine will help white blood cells recognize and kill the cancer cells throughout the body. This vaccine therapy has been tested in hundreds of patients and is very well tolerated. Researchers want to see whether this vaccine, given with enzalutamide, is more effective at treating advanced prostate cancer than enzalutamide alone. Objectives: \- To compare the safety and effectiveness of enzalutamide with and without vaccine therapy for advanced prostate cancer. Key Eligibility:

• Men at least 18 years of age who have advanced castration sensitive prostate cancer.
• Patients must have testosterone within the normal range
• No evidence of metastatic prostate cancer on computed tomography (CT) or Bone scan
• No history of autoimmune diseases
• No previous immunotherapy within 3 years Design:
• Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies will be used to monitor the cancer before treatment.
• Participants will be separated into two groups. One group will have enzalutamide and the study vaccine. The other group will have enzalutamide alone.
• All participants will take enzalutamide once a day. They will take the drug for 3 months. This form of intermittent therapy is common in this population of patients.
• The vaccine group of participants will receive the new study vaccine. They will have a single injection on the first day of the first study cycle. There will be regular booster injections afterward. There will be one injection during the third week of treatment, and one in the fifth week. The vaccine will then be given every 4 weeks until 21 weeks have passed.
• Treatment will be monitored with frequent blood tests and imaging studies.

Conditions

Prostate Cancer

Keywords

Gene Transfer; Androgen Receptor Antagonist; PSA; Immune Response; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Tumor Growth Rate

  Growth rate was measured using the growth rate equation -f(t) = exp (-d\*t) + exp (g\*t) -1 where exp is the base of the natural algorithm, e = 2.7182 and t is days since treatment started. The tumor growth rate equation measures Prostate Specific Antigen (PSA) rise over time. The UOM is unitless because this is a way to measure PSA kinetics.

  7 months

Secondary Outcomes (5)

• Mean Pretreatment Plasma Vascular Endothelial Growth Factor (VEGF) Concentration 30 Days After the Start of Course 1 and Course 2 of Enzalutamide

  30 Days After the Start of Course 1 and Course 2 of Enzalutamide

• Median Testosterone After 84 Days of Enzalutamide

  84 days

• Percent Change in Prostate Specific Antigen (PSA) After 84 Days of Enzalutamide in Course 1

  84 days

• Number of Participants With Serious and 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 43 months and 13 days for Arm A, and 78 months and 6 days for Arm B.

• Median Time Until Prostate Specific Antigen (PSA) Recovery From Baseline Following Course 1 and Course 2 of Enzalutamide

  up to 41 months

Study Arms (2)

Arm A - Enzalutamide for 3 months

EXPERIMENTAL

Enzalutamide for 3 months

Drug: Enzalutamide (Xtandi)

Arm B - Enzalutamide for 3 months + PSA-TRICOM

EXPERIMENTAL

Enzalutamide 3 months + PSA-TRICOM (Prostvac-V/F) on weeks 1, 3, 5, 9,13,17 and 21

Biological: PROSTVAC-F (Fowlpox)/TRICOM; Biological: PROSTVAC-V (Vaccinia)/TRICOM; Drug: Enzalutamide (Xtandi)

Interventions

PROSTVAC-F (Fowlpox)/TRICOM BIOLOGICAL

A recombinant fowlpox virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.

Also known as: PROSTVAC-F/TRICOM

Arm B - Enzalutamide for 3 months + PSA-TRICOM

PROSTVAC-V (Vaccinia)/TRICOM BIOLOGICAL

A recombinant vaccinia virus vector vaccine containing the genes for human prostate specific antigen (PSA) and three co-stimulatory molecules.

Also known as: PROSTVAC-V/TRICOM

Arm B - Enzalutamide for 3 months + PSA-TRICOM

Enzalutamide (Xtandi) DRUG

An androgen receptor inhibitor.

Also known as: Xtandi

Arm A - Enzalutamide for 3 months; Arm B - Enzalutamide for 3 months + PSA-TRICOM

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center, or Walter Reed National Military Medical Center prior to enrollment. If no pathologic specimen is available, patients may enroll with a pathologists report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• B. Biochemical progression defined as follows:
• For patients following definitive radiation therapy: a rise in prostate-specific antigen (PSA) of greater than or equal to 2 ng/mL above the nadir (per Radiation Therapy Oncology Group (RTOG)-American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria).
• For patients following radical prostatectomy: rising PSA after surgical procedure. (Patients must have a PSA greater than or equal to 2ng/ml)
• C. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Karnofsky greater than or equal to 80%).
• D. Patients must have a PSA doubling time of 12 months or less.
• E. Patients must have a rising PSA as confirmed by 3 values done at least 1 week apart and over no less than 1 month.
• F. Recovery from acute toxicity related to prior therapy, including surgery and radiation, or no toxicity greater than or equal to grade 2.
• G. Negative computed tomography (CT) scan/magnetic resonance imaging (MRI) and bone scan for metastatic prostate cancer.
• H. Hematological eligibility parameters (within 16 days before starting therapy):
• Granulocyte count greater than or equal to 1000/mm(3)
• Platelet count greater than or equal to 100,000/mm(3)
• Hemoglobin (Hgb) greater than or equal to 10 g/dL
• I. Biochemical eligibility parameters (within 16 days before starting therapy):
• Hepatic function: bilirubin less than or equal to 1.5 mg/dL (OR in patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0), aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal to 2.5 times upper limit of normal.

You may not qualify if:

• A. Immunocompromised status due to:
• Human immunodeficiency virus (HIV) positivity.
• Active autoimmune diseases such as Addison's disease, Hashimoto s thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Graves 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
• B. Chronic administration (defined as daily or every other day for continued use greater than 14 days) of corticosteroids deemed systemic by investigator within 28 days before the first planned dose of PSA-TRICOM. Use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed.
• C. Serious intercurrent medical illness that, in the judgment of the investigator, would interfere with patient's ability to carry out the treatment program.
• D. History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attack, or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization).
• E. Other medications used for urinary symptoms including 5-alpha reductase inhibitors (finasteride and dutasteride) and alternative medications known to alter PSA (eg phytoestrogens and saw palmetto)
• F. History of prior chemotherapy
• G. History of prior immunotherapy within the last 3 years
• H. Major surgery within 4 weeks prior to enrollment (Day 1 visit).
• I. History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or poxviral vaccines (e.g., vaccinia vaccine)
• J. Known allergy to eggs, egg products, aminoglycoside antibiotics (for example, gentamicin or tobramycin).
• K. History of atopic dermatitis or active skin condition (acute, chronic, exfoliative) that disrupts the epidermis
• L. Previous serious adverse reactions to smallpox vaccination

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 Publications (4)

• Furr BJ. "Casodex" (ICI 176,334)--a new, pure, peripherally-selective anti-androgen: preclinical studies. Horm Res. 1989;32 Suppl 1:69-76. doi: 10.1159/000181315.

  PMID: 2533159 BACKGROUND

• Chen Y, Clegg NJ, Scher HI. Anti-androgens and androgen-depleting therapies in prostate cancer: new agents for an established target. Lancet Oncol. 2009 Oct;10(10):981-91. doi: 10.1016/S1470-2045(09)70229-3.

  PMID: 19796750 BACKGROUND

• Sartor AO, Tangen CM, Hussain MH, Eisenberger MA, Parab M, Fontana JA, Chapman RA, Mills GM, Raghavan D, Crawford ED; Southwest Oncology Group. Antiandrogen withdrawal in castrate-refractory prostate cancer: a Southwest Oncology Group trial (SWOG 9426). Cancer. 2008 Jun;112(11):2393-400. doi: 10.1002/cncr.23473.

  PMID: 18383517 BACKGROUND

• Madan RA, Karzai F, Donahue RN, Al-Harthy M, Bilusic M, Rosner II, Singh H, Arlen PM, Theoret MR, Marte JL, Cordes L, Couvillon A, Hankin A, Williams M, Owens H, Lochrin SE, Chau CH, Steinberg S, Figg WD, Dahut W, Schlom J, Gulley JL. Clinical and immunologic impact of short-course enzalutamide alone and with immunotherapy in non-metastatic castration sensitive prostate cancer. J Immunother Cancer. 2021 Mar;9(3):e001556. doi: 10.1136/jitc-2020-001556.

  PMID: 33664086 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

PROSTVAC; rV-Tricom; enzalutamide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Ravi A. Madan
• Organization: National Cancer Institute

m480i@nih.gov

301-480-7168

Study Officials

• Ravi A Madan, 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: June 7, 2013
• First Posted: June 11, 2013
• Study Start: July 22, 2013
• Primary Completion: September 1, 2019
• Study Completion: February 28, 2020
• Last Updated: September 16, 2020
• Results First Posted: September 16, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)