AzTrials
AzTrials

Prostate CancerPhase 2NCT01867333

Enzalutamide With or Without Vaccine Therapy for Advanced Prostate Cancer

A Phase 2 study testing PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM, PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM and Enzalutamide in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM, PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
57 participants
Where
1 siteUnited States
Study dates
12 Aug 2013to 26 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • Radiographic progression defined as any new or enlarging bone lesions or growing lymph node disease, consistent with prostate cancer OR
  • 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
  • platelets greater than or equal to 100,000/mcL
  • total bilirubin within normal institutional limits; for patients with Gilbert's syndrome, total bilirubin less than or equal to 3.0mg/dL
  • Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamic pyruvic transferase (SGPT) less than or equal to 2.5 times institutional upper limit of normal
  • creatinine within 1.5 X normal institutional limits, OR
  • creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal by Cockcroft-Gault Equation
  • The effects of enzalutamide alone or in combination with PSA-TRICOM on the developing human fetus are unknown. For this reason, men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for three (3) months after the last dose of enzalutamide. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

Who cannot join

  • 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.
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  • 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).
  • Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including the long-term follow-up), or would interfere with the evaluation of the trial endpoints.
  • Patients with prior chemotherapy for nonmetastatic prostate cancer within a year are excluded.
  • Receipt of an investigational agent within 28 days (or 56 days for an antibody-based therapy) before the first planned dose of study drugs. (Immune checkpoint inhibitors that are antibody-based will only require 28 days before enrollment)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension (systolic blood pressure (SBP)>170/ diastolic blood pressure (DBP)>105) or psychiatric illness/social situations within 12 months that would limit compliance with study requirements.
  • Use of herbal products that may decrease PSA levels (e.g., saw palmetto)
  • Any gastrointestinal disease that could hinder the absorption of enzalutamide.
  • Patients who have had chemotherapy for metastatic castration-resistant prostate cancer. (Patients who have had docetaxel for metastatic castration sensitive disease per Chemo-hormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) Data35 may enroll as long as they did not have progressive disease while on docetaxel and are 6 months removed from treatment, with all treatment related toxicities resolving to at least grade 1.)
  • Patients who have received radiation therapy, radionuclide therapy or undergone surgery within certain duration (4 weeks) of enrollment

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Randomized Phase II Trial Combining Vaccine Therapy With PROSTVAC /TRICOM and Enzalutamide vs. Enzalutamide Alone in Men With Metastatic Castration Resistant Prostate Cancer

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.
Read more

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.
Read the detailed description

Background:

  • Enzalutamide is a well-tolerated, modern androgen receptor antagonist (ARA) with more enhanced anti-tumor activity compared to previous ARAs. Phase III trial has demonstrated a 4.8 month improvement in survival and a 37% risk reduction in death in metastatic castration resistant prostate cancer (mCRPC) patients who have had previous docetaxel.
  • PROSTVAC is a therapeutic cancer vaccine which is designed to induce an anti-tumor immune response. In a randomized controlled Phase 2 trial, PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) therapy was associated with a prolongation of survival by 8.5 months in men with metastatic castrate-resistant prostate cancer. An international Phase 3 trial is on-going.
  • Preclinical data has demonstrated that hormonal therapies such as ARAs can enhance the immune response through multiple mechanisms. Specifically, our group has shown that enzalutamide can increase thymic production of na(SqrRoot) ve T-cells, which could be activated by a cancer vaccine. Together, these data provide an important rationale to combine enzalutamide with PSA-TRICOM in mCRPC.
  • Data from the clinical trials with these therapies suggest that they are very well tolerated and without overlapping toxicity.

Objective:

-Determine if prostate-specific antigen (PSA)-TRICOM combined with enzalutamide will increase time to progression (as defined by Prostate Cancer Clinical Trials Working Group 2 criteria, incorporated in section 5.2) in chemotherapy-naive metastatic castration resistant prostate cancer patients compared to enzalutamide alone.

Design:

  • The study will randomize chemotherapy-naive, mCRPC patients to either enzalutamide alone or enzalutamide with PSA-TRICOM. Enzalutamide will be given at the standard dose of 160 mg daily.
  • PSA-TRICOM will be administered identical to the Phase III dosing with vaccine given week 1 (vaccinia-PSA-TRICOM, 2x10(8) units subcutaneously) and then week 3, 5 and then monthly fowlpox-vaccine (1x10(9) units subcutaneously).
  • After completing 6 months of vaccine, fowlpox-vaccine (1x10(9) units subcutaneously will be administered every 3 months. Patients will be treated until radiographic progression on scans using Prostate Cancer Working Group Criteria.

Eligibility:

  • mCRPC patients with rising PSA or progressive disease despite castration levels of testosterone.
  • Chemotherapy-na(SqrRoot) ve with minimal or no symptoms related to prostate cancer.
  • Patients with history of autoimmune disease, brain/leptomeningeal metastasis, a second malignancy within 3 years of enrollment, or a severe co-morbid condition will be excluded.
  • Patients who have received abiraterone will be excluded
  • Patients will be stratified based on previous immunotherapy used as cancer treatment.
Conditions
Prostate Cancer
Being tested
PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM, PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM, Enzalutamide
Keywords
Immunotherapy, Gene Transfer, Androgen Receptor Antagonist, PSA, Immune Response
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOMBiological

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

  • PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOMBiological

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

  • EnzalutamideBiological

    Also called Xtandi

    An androgen receptor inhibitor.

Study groups in NCT01867333
Study groupRoleWhat they receive
Arm 1 - Enzalutamide aloneExperimentalEnzalutamide alone. Enzalutamide will be given at the standard dose of 160 mg daily.
Receives: Biological: Enzalutamide
Arm 2 - Enzalutamide with Prostate-Specific Antigen (PSA)-TRICOMExperimentalEnzalutamide 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).
Receives: Biological: PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM; Biological: PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM; Biological: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Median follow-up of 55.4 months

Secondary outcomes (2)

  1. Overall Survival

    Overall survival is defined as the date of on-study to the date of death from any cause or last follow up.

    Measured: Median potential follow-up of 68.5 months

  2. Time to Prostate-specific Antigen (PSA) Progression

    PSA progression is defined by a sequence of rising values separated by >1 week (2 separate increasing values over a minimum of 2ng/ml or 25% higher (Prostate Cancer Clinical Trials Working Group (PCWG2) PSA eligibility criteria).

    Measured: Median follow-up of 55.4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2013 (estimated)
  2. Study start12 Aug 2013
  3. Primary completion28 Sep 2022
  4. Study completion26 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01867333
Sponsor's protocol ID
130146
Other IDs
13-C-0146
Status last verified
Sep 2023
First submitted
30 May 2013
Last updated
26 Sep 2023
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).

Publications

  • 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.

    PubMed 20100959

  • 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.

    PubMed 19548854

  • 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.

    PubMed 22894553

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -F/TRICOM, PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM and Enzalutamide in people with Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Progression (TTP) (time frame: Median follow-up of 55.4 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01867333, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2023.

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