Enzalutamide With or Without Vaccine Therapy for Advanced Prostate Cancer

NCT01867333 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13014613-C-0146
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Enzalutamide is a hormone therapy that is used to treat advanced prostate cancer. It is given after chemotherapy and surgery to help the body destroy the cancer cells. A new possible way of treating prostate cancer is using a vaccine that may help stimulate the immune system. It will help white blood cells recognize and kill the cancer cells in and around the prostate. 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. Eligibility: \- Men at least 18 years of age who have advanced castration-resistant prostate cancer. 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 during 4-week cycles of treatment.
• Treatment will be monitored with frequent blood tests and imaging studies. Participants will continue to take the study drug for as long as the cancer does not grow, and the side effects are not severe.
• The vaccine group of participants will also have 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 on day 15 of the first cycle, the first day of the second cycle. The vaccine will then be given every 4 weeks for the next four cycles, and then every 12 weeks (every 3 cycles) thereafter. Participants will continue to have the study vaccine for as long as the cancer does not grow, and the side effects are not severe.

Conditions

Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Time to Progression (TTP)

  Time to progression is defined as the duration of time from start of treatment to time of disease progression. Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions can also be considered progression if they meet the size criteria for target lesions.

  Median follow-up of 55.4 months

Secondary Outcomes (2)

• Overall Survival

  Median potential follow-up of 68.5 months

• Time to Prostate-specific Antigen (PSA) Progression

  Median follow-up of 55.4 months

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 109 months and 15 days and 110 months and 13 days for Arm 1 and Arm 2 respectively.

Study Arms (2)

Arm 1 - Enzalutamide alone

EXPERIMENTAL

Enzalutamide alone. Enzalutamide will be given at the standard dose of 160 mg daily.

Biological: Enzalutamide

Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOM

EXPERIMENTAL

Enzalutamide with PSA-TRICOM. Enzalutamide will be given at the standard dose of 160 mg daily with vaccine given week 1 (vaccinia-PSA-TRICOM, 2x10(8) infectious units subcutaneously) and then week 3, 5 and then monthly fowlpox-vaccine (1x10(9) infectious units subcutaneously).

Biological: PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM; Biological: PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM; Biological: Enzalutamide

Interventions

PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM BIOLOGICAL

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

Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOM

PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM BIOLOGICAL

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

Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOM

Enzalutamide BIOLOGICAL

An androgen receptor inhibitor.

Also known as: Xtandi

Arm 1 - Enzalutamide alone; Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOM

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed prostate cancer confirmed by either the Laboratory of Pathology at the National Institutes of Health (NIH) Clinical Center or Walter Reed National Military Medical Center at Bethesda prior to starting this study. If no pathologic specimen is available, patients may enroll with a pathologist's report showing a histological diagnosis of prostate cancer and a clinical course consistent with the disease.
• Castrate testosterone level (\<50ng/dl or 1.7nmol /L)
• Metastatic disease documented by one of the following:
• Metastatic bone disease on an imaging study, or
• Soft tissue disease documented by computed tomography (CT)/magnetic resonance imaging (MRI), or
• Progressive disease at study entry defined as one or more of the following criteria occurring in the setting of castrate levels of testosterone:
• i. Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR
• ii. Prostate-specific antigen (PSA) progression defined by sequence of rising values separated by \>1 week (2 separate increasing values over a minimum of 2ng/ml (Prostate Cancer Clinical Trials Working Group (PCWG2) PSA eligibility criteria). If patients had been on flutamide, PSA progression is documented 4 weeks or more after withdrawal.
• The requirement for a 4-6 weeks withdrawal period following discontinuation of flutamide, nilutamide or bicalutamide only applies to patients who have been on these drugs for at least the prior 6 months. For all other patients they must stop bicalutamide, nilutamide or flutamide the day prior to enrollment.
• Asymptomatic or mildly symptomatic from prostate cancer; no use of regularly scheduled opiate analgesics for prostate cancer-related pain
• Patients must agree to continue to continuation of androgen deprivation therapy (ADT) with a gonadotropin-releasing hormone analogue/antagonist or bilateral orchiectomy
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky greater than or equal to 80%).
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to 1,500/mcL

You may not qualify if:

• Patients who are immunocompromised as listed as follows:
• Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects
• Chronic administration (defined as daily or every other day for continued use \>14 days) of systemic corticosteroids (including steroid eye drops) or other immune suppressive drugs, within 28 days before the first planned dose of PSA-TRICOM. Nasal, or inhaled steroid, and topical steroid creams for small body areas are not excluded.
• Patients who have undergone allogeneic peripheral stem cell transplantation, or solid organ transplantation requiring immunosuppression
• History of splenectomy
• History of, or active autoimmune disease (such as Autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosis, Sjogrens syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addisons disease, Hashimoto's thyroiditis, Crohn's or Grave's disease). Patients with type 1 diabetes mellitus or vitiligo are not excluded if the condition is well controlled.
• Patients with a history of brain/leptomeningeal metastasis
• Patients who have been treated with abiraterone will be excluded
• Patients with history of seizure as an adult including febrile seizure or any condition that may predispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). Also, current or prior treatment with anti-epileptic medications for the treatment of seizures or history of loss of consciousness. Also transient ischemic attack within 12 months prior to randomization will not be permitted.
• Patients with second malignancy within 3 years of enrollment; Patients curatively treated non-melanoma skin cancers or carcinoma in situ of the bladder, are not excluded.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or 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 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 eczematoid skin disorders, or (d) immunocompromised individuals, such as those with human immunodeficiency virus (HIV).

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, Manson K, Panicali DL, Laus R, Schlom J, Dahut WL, Arlen PM, Gulley JL, Godfrey WR. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010 Mar 1;28(7):1099-105. doi: 10.1200/JCO.2009.25.0597. Epub 2010 Jan 25.

  PMID: 20100959 BACKGROUND

• Madan RA, Arlen PM, Mohebtash M, Hodge JW, Gulley JL. Prostvac-VF: a vector-based vaccine targeting PSA in prostate cancer. Expert Opin Investig Drugs. 2009 Jul;18(7):1001-11. doi: 10.1517/13543780902997928.

  PMID: 19548854 BACKGROUND

• Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Flechon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. doi: 10.1056/NEJMoa1207506. Epub 2012 Aug 15.

  PMID: 22894553 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page
• http://www.clinicaltrials.gov

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

PROSTVAC; 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: Ravi A. Madan
• Organization: National Cancer Institute

rm480i@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: May 30, 2013
• First Posted: June 4, 2013
• Study Start: August 12, 2013
• Primary Completion: September 28, 2022
• Study Completion: October 26, 2022
• Last Updated: September 26, 2023
• Results First Posted: September 26, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as the database is active.
• Access Criteria: Clinical data will be made available via subscription to Translational Research Information System (BTRIS) and with permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians

Locations

US (1)