Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01875250
First received: June 7, 2013
Last updated: March 14, 2014
Last verified: February 2014
  Purpose

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-resistant prostate cancer.
  • Patients must have testosterone within the normal range
  • No evidence of metastatic prostate cancer on CT or Bone scan
  • No history of autoimmune diseases
  • No previous immunotherpy 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.

Condition Intervention Phase
Prostate Cancer
Biological: PROSTVAC-F/TRICOM
Biological: PROSTVAC-V/TRICOM
Drug: Enzalutamide (Xtandi)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Enzalutamide in Combination With PSA-TRICOM in Patients With Non-Metastatic Castration Sensitive Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Decrease in tumor re-growth rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immune response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Determine impact on PSA [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 38
Study Start Date: May 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Enzalutamide alone
Drug: Enzalutamide (Xtandi)
160 mg daily for 3 months
Active Comparator: Arm B
Enzalutamide + PSA-TRICOM
Biological: PROSTVAC-F/TRICOM
Weeks 3, 5, 9, 13, 17, and 21
Biological: PROSTVAC-V/TRICOM
Week 1

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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 pathologist s 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 PSA of greater than or equal to 2 ng/mL above the nadir (per RTOG-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. 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 CT scan/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)

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), AST and ALT less than or equal to 2.5 times upper limit of normal.

J. No other active malignancies within the past 36 months (with the exception of nonmelanoma skin cancers or carcinoma in situ of the bladder) or life-threatening illnesses

K. Willing to travel to the NIH for follow-up visits.

L. 18 years of age or older.

M. Able to understand and sign informed consent.

N. Baseline testosterone greater than or equal to lower limit of normal.

O. PSA less than or equal to 20 ng/mL.

P. The effects of enzalutamide, PSA-TRICOM or the combination 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. 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.

EXCLUSION CRITERIA:

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 Grave s disease. Patients with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and 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

M. Unable to avoid close contact or household contact with the following highrisk individuals for three weeks after the Day 1 vaccination: (a) children 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 HIV.

N. Receipt of an investigational agent within 30 days (or 60 days for an antibodybased therapy) before the first planned dose of study drugs.

O. Patients who test positive for HBV or HCV

P. Use of herbal products that may decrease PSA levels (e.g. saw palmetto)

Q. Any gastrointestinal disease that could hinder the absorption of enzalutamide

R. Uncontrolled hypertension (SBP> 170/ DBP> 105)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01875250

Contacts
Contact: Laura Otten, R.N. (301) 451-1228 ottenl@mail.nih.gov
Contact: Ravi A Madan, M.D. (301) 496-3493 rm480i@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Ravi A Madan, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01875250     History of Changes
Other Study ID Numbers: 130153, 13-C-0153
Study First Received: June 7, 2013
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Gene Transfer
Androgen Receptor Antagonist
PSA
Immune Response
Immunotherapy

Additional relevant MeSH terms:
Genital Diseases, Male
Prostatic Diseases
Prostatic Neoplasms
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Metronidazole
Anti-Infective Agents
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014