Sequential Vaccinations in Prostate Cancer Patients

NCT00060528 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 03017603-C-0176
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Background: " Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and follows lung cancer as the leading cause of cancer death. " Vaccine strategies represent a novel therapeutic approach in the treatment for prostate cancer. One potential target for a prostate cancer vaccine is prostatic specific antigen (PSA), due to its restricted expression on prostate cancer and normal prostatic epithelial cells. Objectives: " The primary objective is to determine the impact of granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant fowlpox granulocyte-macrophage colony stimulating factor (rF-GM-CSF) on the immunologic response in patients treated with these vaccines. " Secondary - to determine the change in prostatic specific antigen (PSA)-specific T cells in patients treated with these vaccines using enzyme linked immunosorbent spot (ELISPOT) assay analysis. " To document any objective anti-tumor responses that may occur. Eligibility: " Patients must have androgen insensitive metastatic prostate cancer. " All patients will have received and progressed on hormonal therapy. " Must have objective evidence of metastasis or relapsing local disease. Therefore, must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies. " Must have a life expectancy of more than 6 months and Eastern Cooperative Oncology Group (ECOG) status of 0 to 2. "Patients must be human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2+). " Granulocyte count greater than or equal to 1,500/mm\^3, Platelet greater than or equal to 100,000/mm\^3, hemoglobin (Hgb) greater than or equal to 10Gm/dL, Lymphocyte count greater than or equal to 500/mm\^3 ;Bilirubin less than 1.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5x upper limit of normal (ULN),Creatinine Clearance greater than or equal to 60 " No significant cardiac disease, no significant pulmonary disease, no serious inter-current medical illness. Design: " Cohorts three, four and five will provide safety data combining cohort two with rGM-CSF as well as two doses of rFGM-CSF respectively. "This study will be conducted as a small, randomized pilot study to compare the immunologic effects of the above vaccine strategy alone, with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), or with either of 2 doses of fowlpox-GM-CSF. "This study will consist of 4 randomized arms of 8 patients each, all of whom are HLA-A2+. The maximum accrual to the trial should be 62.

Conditions

Prostatic Neoplasms

Keywords

Immunotherapy; Cytokines; Immune Assays; Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With an Immune Response

  Immune response is defined as an enhanced PSA specific T-cell immune response greater than or equal to twofold post-vaccination. Peripheral blood mononuclear cells (PBMCs) were collected by apheresis prior to treatment with vaccination and after approximately three months of therapy.

  48 months

Secondary Outcomes (4)

• Percent of Participants With a Decrease (i.e. Greater Than or Equal to 30%) in PSA Levels

  53 months

• Number of Participants With an Objective Response

  53 months

• Overall Survival

  50 months

• The Number of Participants With Adverse Events

  77.5 months

Study Arms (4)

no GM

EXPERIMENTAL

No granulocyte macrophage colony stimulating factor (GM-CSF) was given

Drug: Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM)

Rec-hGM

EXPERIMENTAL

Recombinant human GM-CSF (Sargramostim) was administered at 100mcg/day on days 1-4 following each vaccine. Given subcutaneously (s.c.) at site of vaccine.

Drug: Recombinant Vaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM); Drug: Recombinant Human GM-CSF

rF-GM (10^7pfu)

EXPERIMENTAL

recombinant fowlpox GM-CSF was given on day one at 10\^7 in last two arms. Given subcutaneously (s.c.) at site of vaccine.

Drug: Recombinant Fowlpox-GM-CSF; Drug: Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM); Drug: Recombinant Human GM-CSF

rF-GM (10^8)

EXPERIMENTAL

recombinant fowlpox GM-CSF was given on day one at 10\^8 in last two arms. Given subcutaneously (s.c.) at site of vaccine.

Drug: Recombinant Fowlpox-GM-CSF; Drug: Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM); Drug: Recombinant Human GM-CSF

Interventions

Recombinant Fowlpox-GM-CSF DRUG

Also known as: rF-GMCSF

rF-GM (10^7pfu); rF-GM (10^8)

Recombinant Fowlpox-PSA (L155)-TRICOM (PROSTVAC-F/TRICOM) DRUG

Also known as: PROSTVAC-F (fowlpox)/TRICOM

no GM; rF-GM (10^7pfu); rF-GM (10^8)

Recombinant Vaccinia-PSA (L155)-TRICOM (PROSTVAC-V/TRICOM) DRUG

Rec-hGM

Recombinant Human GM-CSF DRUG

Rec-hGM; rF-GM (10^7pfu); rF-GM (10^8)

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 histopathological documentation of prostate cancer confirmed in the Laboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), or National Naval Medical Center (NNMC) prior to starting this study.
• If no pathologic specimen is available to the NCI or NNMC, patients may enroll with a pathologist's report showing a histologic diagnosis of prostate cancer and a clinical course consistent with the disease.
• Patients must have androgen insensitive metastatic prostate cancer.
• Progression must be documented by at least one of the following parameters:
• All patients must have received standard of care (hormonal) treatment before entering the trial.
• All patients will have received and progressed on hormonal therapy for metastatic prostate carcinoma.
• All subjects must have objective evidence of metastasis or relapsing local disease to be eligible for this Phase I trial; therefore, they must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies, as defined below.
• i. Two consecutively rising prostatic specific antigen (PSA) levels, separated by at least 1 week, with at least one measurement that is 50% above the nadir reached after the last therapeutic maneuver (as long as the last measurement is 5 ng/ml or greater), and
• ii. At least one lesion consistent with metastatic cancer on Technetium (Tc)-99 whole body scintigraphy, and/or
• iii. Soft-tissue metastases as measured by appropriate modalities (i.e., imaging, palpation).
• Patients must have a life expectancy of more than 6 months.
• Patients must have a performance status of 0 to 2 according to the Eastern Cooperative Oncology Group (ECOG) criteria.
• Patients must have recovered from any acute toxicity related to prior therapy, including surgery, and radiation (treatment must have been completed at least 4 weeks prior to being eligible for the study).
• Patients who are responding to hormonal therapy are not eligible until evidence of disease progression.
• Hematological eligibility parameters (within 16 days of starting therapy):

You may not qualify if:

• Prior splenectomy.
• Concurrent steroid use, except topical steroids or inhaled steroid use.
• The recombinant vaccinia vaccine should not be administered if the following apply to either recipients or, for at least 3 weeks after vaccination, their close household contacts:
• 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 under 5 years of age; and immunodeficient or immunosuppressed persons (by disease or therapy), including HIV infection.
• Close household contacts are those who share housing or have close physical contact.
• Patients with known allergy to eggs.
• Other serious intercurrent illness.
• Patients with brain metastases.
• Patients with a history of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment) or New York Heart Association class II-IV congestive heart failure.
• Patients on antiandrogen therapy must undergo antiandrogen 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.
• Prior treatments with vaccine expressing PSA are NOT eligible.
• Patients with significant autoimmune disease that is active or potentially life threatening if activated.
• Patients with clinically significant cardiomyopathy requiring treatment should be excluded from protocol eligibility at this time.

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 (9)

• Correale P, Walmsley K, Nieroda C, Zaremba S, Zhu M, Schlom J, Tsang KY. In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen. J Natl Cancer Inst. 1997 Feb 19;89(4):293-300. doi: 10.1093/jnci/89.4.293.

  PMID: 9048833 BACKGROUND

• Vergati M, Cereda V, Madan RA, Gulley JL, Huen NY, Rogers CJ, Hance KW, Arlen PM, Schlom J, Tsang KY. Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination. Cancer Immunol Immunother. 2011 Feb;60(2):197-206. doi: 10.1007/s00262-010-0927-9. Epub 2010 Oct 26.

  PMID: 20976449 BACKGROUND

• Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Schlom J, Tsang KY. Enhanced functionality of CD4+CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res. 2008 Feb 15;14(4):1032-40. doi: 10.1158/1078-0432.CCR-07-2056.

  PMID: 18281535 BACKGROUND

• Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW, Cereda V, Vergati M, Steinberg SM, Halabi S, Jones E, Chen C, Parnes H, Wright JJ, Dahut WL, Schlom J. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother. 2010 May;59(5):663-74. doi: 10.1007/s00262-009-0782-8. Epub 2009 Nov 5.

  PMID: 19890632 BACKGROUND

• Stein WD, Gulley JL, Schlom J, Madan RA, Dahut W, Figg WD, Ning YM, Arlen PM, Price D, Bates SE, Fojo T. Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin Cancer Res. 2011 Feb 15;17(4):907-17. doi: 10.1158/1078-0432.CCR-10-1762. Epub 2010 Nov 24.

  PMID: 21106727 BACKGROUND

• Smith HA, Maricque BB, Eberhardt J, Petersen B, Gulley JL, Schlom J, McNeel DG. IgG responses to tissue-associated antigens as biomarkers of immunological treatment efficacy. J Biomed Biotechnol. 2011;2011:454861. doi: 10.1155/2011/454861. Epub 2010 Dec 19.

  PMID: 21197272 BACKGROUND

• Kim JW, Madan RA, Gulley JL. Initial PSA oscillations precede prolonged stable disease in a patient treated with a therapeutic cancer vaccine. Clin Genitourin Cancer. 2012 Mar;10(1):43-6. doi: 10.1016/j.clgc.2011.09.003. Epub 2011 Oct 21. No abstract available.

  PMID: 22019260 BACKGROUND

• Arlen PM, Skarupa L, Pazdur M, Seetharam M, Tsang KY, Grosenbach DW, Feldman J, Poole DJ, Litzinger M, Steinberg SM, Jones E, Chen C, Marte J, Parnes H, Wright J, Dahut W, Schlom J, Gulley JL. Clinical safety of a viral vector based prostate cancer vaccine strategy. J Urol. 2007 Oct;178(4 Pt 1):1515-20. doi: 10.1016/j.juro.2007.05.117. Epub 2007 Aug 16.

  PMID: 17707059 RESULT

• Huang J, Jochems C, Talaie T, Anderson A, Jales A, Tsang KY, Madan RA, Gulley JL, Schlom J. Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role. Blood. 2012 Oct 11;120(15):3030-8. doi: 10.1182/blood-2012-05-427799. Epub 2012 Aug 28.

  PMID: 22932804 DERIVED

Related Links

• Medline Plus
• Drug Information Portal
• U.S. FDA Resources

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

PROSTVAC; Granulocyte-Macrophage Colony-Stimulating Factor

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

Results Point of Contact

• Title: James L. Gulley, M.D.
• Organization: National Cancer Instititute (NCI), National Institutes of Health (NIH)

gulleyj@mail.nih.gov

301-435-2956

Study Officials

• James L Gulley, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• 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 7, 2003
• First Posted: May 7, 2003
• Study Start: May 22, 2003
• Primary Completion: March 7, 2006
• Study Completion: June 8, 2009
• Last Updated: October 26, 2017
• Results First Posted: February 23, 2012

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)