Vaccine Therapy With PROSTVAC/TRICOM and Flutamide Versus Flutamide Alone to Treat Prostate Cancer

NCT00450463 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 07010707-C-0107
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

Brief Summary

Background:

• Flutamide is an approved drug for prostate cancer that blocks the effects of testosterone on prostate cancer cells and may slow the progression of the disease.
• The vaccine in this study consists of a priming vaccine called PROSTVAC (rilimogene galvacirepvec/rilimogene glafolivec) -V/TRICOM (triad of costimulatory molecules), made from vaccinia virus, and a boosting vaccine called PROSTVAC-F/TRICOM, made from fowlpox virus. DNA (Deoxyribonuceic acid) is inserted into the priming and boosting vaccine viruses to cause production of proteins that enhance immune activity and also to produce prostate specific antigen (PSA) a protein that is normally produced by the patients tumor cells.
• GM-CSF (granulocyte macrophage colony stimulating factor), given along with the vaccine, is a chemical that boosts the immune system. It is used in this study to try to increase the usefulness of the vaccine by increasing the number of immune cells at the vaccination site. Objectives:
• To determine if treatment with a prostate cancer vaccine plus flutamide is more effective than flutamide alone in delaying disease progression in patients with prostate cancer. Eligibility:
• Patients 18 years of age and older with androgen-insensitive prostate cancer that has not spread beyond the prostate gland.
• Patients with a rising PSA (prostatic specific antigen) who have already been treated with anti-iandrogen therapy (either bicalutamide or nilutamide). Design:
• There are two treatment groups in this study. Group A receives only flutamide; group B receive flutamide plus vaccine.
• Patients in both groups receive flutamide by mouth three times a day.
• Patients in group B receive PROSTVAC-V/TRICOM on day 1 and PROSTVAC-F/TRICOM on day 29 and again every 4 weeks. All vaccines are given as injections under the skin.
• Patients have blood tests for PSA levels every month and scans every 3 months until the disease worsens.
• After 3 months of therapy, patients receiving in group A (flutamide alone) may cross over to receive vaccine if they develop a rising PSA and scans show no sign of disease spread. Patients in group B (flutamide plus vaccine) stop flutamide and may continue vaccine therapy. At this point patients may continue to receive treatment until the disease progresses or PSA levels rise....

Conditions

Prostate Cancer

Keywords

Immunotherapy; Hormonal Therapy; Combination Therapy; Prostate Specific Antigen; Immunoassay; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Time to Treatment Failure

  Time to treatment failure is defined as a rising Prostatic Specific Antigen (PSA) (Bubley criteria, JCO 1999), development of metastatic disease, or removal from treatment due to excessive toxicity) compared to patients receiving flutamide alone. Normal PSA is 4.0 ng/mL or lower.

  Median Potential Follow-up of 46.7 months

Secondary Outcomes (3)

• Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

  Median Potential Follow-up of 46.7 months

• Number of Participants With Prostatic Specific Antigen (PSA) Response

  Median potential follow-up for all patients is 46.7 months

• Percentage of Participants With Antigen Specific Immune Responses Against Prostatic Specific Antigen (PSA)

  3 months

Study Arms (2)

Flutamide Alone

ACTIVE COMPARATOR

Patients receive flutamide orally 3 times a day on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising prostatic specific antigen (PSA) levels) without metastatic disease (as evidenced on scans), may receive vaccine treatment as defined in arm II beginning 4 weeks after flutamide therapy is discontinued.

Drug: Flutamide (Eulexin)

Flutamide + Vaccine + Sargramostim

EXPERIMENTAL

Patients receive flutamide orally 3 times a day on days 1-28. Patients also receive recombinant vaccinia PSA vaccine subcutaneously (SC) on day 1 of course 1 only and recombinant fowlpox PSA vaccine SC on day 1 of all subsequent courses. Patients receive sargramostim (GM-CSF) SC on days 1-4. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After 3 months of treatment, patients who do not develop clinical progression, but develop biochemical recurrence (e.g., rising PSA levels), discontinue flutamide but may continue to receive vaccine treatment.

Drug: Sargramostim (GM-CSF, Leukine); Drug: Flutamide (Eulexin); Biological: PROSTVAC-F/ TRICOM; Biological: PROSTVAC-V/TRICOM

Interventions

Sargramostim (GM-CSF, Leukine) DRUG

A recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) produced by recombinant deoxyribonucleic acid (DNA) technology in yeast Saccharomyces cerevisiae). Sargramostim is a 127 amino acid glycoprotein, altered from the native, natural human GM-CSF molecule; the position 23 arginine has been replaced with a leucine to facilitate the expression of the protein in yeast.

Also known as: GM-CSF

Flutamide + Vaccine + Sargramostim

Flutamide (Eulexin) DRUG

Orally administered, nonsteroidal, competitive antagonist of testosterone and other androgens at androgenic receptors and may alter the nuclear translocation of the androgen/receptor complex.

Also known as: Eulexin

Flutamide + Vaccine + Sargramostim; Flutamide Alone

PROSTVAC-F/ TRICOM BIOLOGICAL

A recombinant fowlpox virus vector vaccine containing the genes for human PSA and three costimulatory molecules.

Also known as: PROSTVAC-F (rilimogene galvacirepvec/rilimogene glafolivec)/TRICOM (triad of costimulatory molecules

Flutamide + Vaccine + Sargramostim

PROSTVAC-V/TRICOM BIOLOGICAL

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

Flutamide + Vaccine + Sargramostim

Eligibility Criteria

• Age: 18 Years - 110 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 prior to starting this study. 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. Must have non-metastatic androgen insensitive prostate cancer with a rising PSA (prostatic specific antigen) with castrate levels of testosterone and no evidence of metastatic disease on CT (computed tomography) scan or bone scan. A rising PSA is defined as two consecutively rising PSA levels, separated by at least 1 month apart, with the last measurement that is greater than 1ng/ml. Patients on nilutamide therapy must undergo nilutamide withdrawal for at least 4 weeks and still show evidence of a rising PSA. Following treatment with bicalutamide, patients must undergo withdrawal for at least 6 weeks and still show evidence of a rising PSA.
• C. Life expectancy greater than or equal to 6 months.
• D. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
• E. No systemic steroid or steroid eye drop use within 2 weeks prior to initiation of experimental therapy.
• F. Hematological eligibility parameters:
• Granulocyte count greater than or equal to 1,500/mm(3).
• Platelet count greater than or equal to 100,000/mm(3)
• Hgb (Hemoglobin) greater than or equal to 9 Gm/dL
• Lymphocyte count greater than or equal to 500/mm(3).
• G. Biochemical eligibility parameters (within 16 days of starting therapy)
• Hepatic function: Bilirubin less than or equal to 1.5 mg/dl, OR patients with Gilbert's syndrome, a total bilirubin less than or equal to 3.0 mg/dL, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) less than 2.5 times upper limit of normal
• H. No other active malignancies within the past 3 years (with the exception of non-melanoma skin cancers or carcinoma in situ of the bladder) or life threatening illnesses.
• I. Willing to travel to the NIH for follow-up visits.
• J. 18 years of age or greater.

You may not qualify if:

• A. Patients should have no evidence of being immunocompromised as listed below.
• Human immunodeficiency virus positivity due to the potential for decreased tolerance and may be at risk for severe side effects.
• Concurrent use of topical steroids (including steroid eye drops) or systemic steroids. Nasal or inhaled steroid use is permitted.
• Patients who have undergone allogenic peripheral stem cell transplantation or solid organ transplantation requiring immunosuppression.
• B. Patients who test positive for active Hepatitis B or Hepatitis C infection.
• C. Patients should have no autoimmune diseases that have required treatment such as, Addison's disease, Hashimoto's thyroiditis, or systemic lupus erythematous, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome, active Grave's disease.
• D. History of allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen.
• E. Do not administer the recombinant vaccinia vaccine if the recipient, or for at least three weeks after vaccination, their close household contacts (close household contacts are those who share housing or have close physical contact) are: persons with active or a history of eczema or other eczematoid skin disorders; those with other acute, chronic or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; pregnant or nursing women; children 3 years of age and under; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV (human immunodeficiency virus) infection.
• F. Serious intercurrent medical illness (e.g., one that requires treatment) which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis.
• G. Patients with cardiac disease that have fatigue, palpitation, dyspnea or angina with ordinary physical activity (New York Heart Association class 2 or greater) are not eligible.
• H. Patients with a history of congestive heart failure or who have objective evidence of congestive heart failure by physical exam or imaging are not eligible.
• I. Patients with pulmonary disease that have fatigue or dyspnea with ordinary physical activity are not eligible.
• J. Concurrent chemotherapy.
• K. No known brain metastasis, or with a history of seizures, encephalitis, or multiple sclerosis.
• L. Patients with a serious hypersensitivity reaction to egg products are not eligible.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Related Publications (4)

• Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30. doi: 10.3322/canjclin.55.1.10.

  PMID: 15661684 BACKGROUND

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

  PMID: 10655437 BACKGROUND

• Dillioglugil O, Leibman BD, Kattan MW, Seale-Hawkins C, Wheeler TM, Scardino PT. Hazard rates for progression after radical prostatectomy for clinically localized prostate cancer. Urology. 1997 Jul;50(1):93-9. doi: 10.1016/S0090-4295(97)00106-4.

  PMID: 9218025 BACKGROUND

• Madan RA, Bilusic M, Stein MN, Donahue RN, Arlen PM, Karzai F, Plimack E, Wong YN, Geynisman DM, Zibelman M, Mayer T, Strauss J, Chen G, Rauckhorst M, McMahon S, Couvillon A, Steinberg S, Figg WD, Dahut WL, Schlom J, Gulley JL. Flutamide With or Without PROSTVAC in Non-metastatic Castration Resistant (M0) Prostate Cancer. Oncologist. 2023 Jul 5;28(7):642-e561. doi: 10.1093/oncolo/oyad058.

  PMID: 37134294 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Flutamide; PROSTVAC; Benchmarking

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)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Management Audit; Organization and Administration; Health Services Administration; Program Evaluation; Quality of Health Care; Quality Assurance, Health Care; Health Care Quality, Access, and Evaluation; Health Care Evaluation Mechanisms

Limitations and Caveats

Eleven patient cross-over group have no statistical plan in the protocol for analysis, highlighting their exploratory nature.

Results Point of Contact

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

ravi_madan@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: March 20, 2007
• First Posted: March 22, 2007
• Study Start: February 23, 2007
• Primary Completion: April 27, 2017
• Study Completion: June 8, 2017
• Last Updated: November 29, 2018
• Results First Posted: November 26, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)