Vaccine Therapy With or Without Sargramostim in Treating Patients With Metastatic Prostate Cancer

Condition(s) targeted: Recurrent Prostate Cancer; Stage IV Prostate Cancer

Intervention: fowlpox-PSA-TRICOM vaccine (Drug); recombinant fowlpox GM-CSF vaccine (Drug); sargramostim (Drug); vaccinia-PSA-TRICOM vaccine (Drug); biological therapy (Procedure); non-specific immune-modulator therapy (Procedure); recombinant viral vaccine (Procedure); vaccine therapy (Procedure)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
Philip M. Arlen, MD, Principal Investigator, Affiliation: National Cancer Institute (NCI)

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may kill more tumor cells.

PURPOSE: This phase I/II trial is studying five different vaccine therapy regimens with or without sargramostim and comparing them to see how well they work in treating patients with metastatic prostate cancer.

Official title: Phase I/II Randomized Pilot Study of Sequential Vaccination With Vaccinia-PSA-TRICOM Vaccine and Fowlpox-PSA-TRICOM Vaccine With or Without Sargramostim (GM-CSF) or Fowlpox-GM-CSF in Patients With Metastatic Prostate Cancer (Phase I Closed to Accrual as of 6/2/04.)

Study design: Treatment

Detailed description: OBJECTIVES:

- Determine the safety and toxicity of sequential vaccination with vaccinia-PSA-TRICOM

vaccine and fowlpox-PSA-TRICOM vaccine in patients with metastatic prostate cancer. (Phase I closed to accrual as of 6/2/04.)

- Determine the impact of sargramostim (GM-CSF) and fowlpox-GM-CSF on immunologic response

in patients treated with these vaccines.

- Determine the change in prostate-specific antigen-specific T cells in patients treated

with these vaccines.

- Determine objective antitumor response in patients treated with these vaccines.

OUTLINE: This is a pilot phase I dose-escalation study (phase I closed to accrual as of 6/2/04) followed by a randomized phase II study.

- Cohorts of 3-6 patients are sequentially assigned to 1 of 5 treatment regimens to

determine the optimal regimen. The optimal regimen is defined as the regimen preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

- Regimen A: Patients receive fowlpox-PSA-TRICOM vaccine (F-PSA-TRI) subcutaneously (SC)

on days 1, 29, and 57.

- Regimen B: Patients receive vaccinia-PSA-TRICOM vaccine (VPSA-TRI) SC on day 1 and

F-PSA-TRI SC on days 29 and 57.

- Regimen C: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and sargramostim

(GM-CSF) SC on days 1-4, 29-32, and 57-60.

- Regimen D: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and

fowlpox-sargramostim (rf-GM-CSF) SC on days 1, 29, and 57.

- Regimen E: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B and a higher dose of

rf-GM-CSF as in regimen D.

- Patients are randomized to 1 of 4 treatment arms, based on the assumption that all 5

regimen levels in phase I are completed.

- Arm I: Patients receive VPSA-TRI and F-PSA-TRI as in regimen B.

- Arm II: Patients receive VPSA-TRI, F-PSA-TRI, and GM-CSF as in regimen C.

- Arm III: Patients receive VPSA-TRI, F-PSA-TRI, and rf-GM-CSF as in regimen D.

- Arm IV: Patients receive VPSA-TRI, F-PSA-TRI, and rf-GM-CSF as in regimen E. Patients in

both phases who do not have disease progression after day 85 may receive monthly F-PSA-TRI vaccinations for 12 weeks, according to their assigned treatment arm. Patients are re-evaluated on day 170 and receive an additional F-PSA-TRI vaccination with subsequent F-PSA-TRI vaccinations every 12 weeks thereafter in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually for 15 years.

PROJECTED ACCRUAL: A maximum of 62 patients (up to 30 for phase I [closed to accrual as of 6/2/04] and a total of 32 [8 per treatment arm] for phase II) will be accrued for this study within 2 years.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed prostate cancer, meeting the following criteria:

- Metastatic disease

- Androgen insensitive

- Progression after prior standard hormonal therapy for metastatic prostate cancer

- Prior antiandrogen therapy requires a rising prostate-specific antigen (PSA) after

withdrawal of at least 4 weeks

- Prior bicalutamide therapy requires a rising PSA after withdrawal of at least 6 weeks

- Objective evidence of metastasis or relapsing local disease as evidenced by a rising

PSA and at least 1 of the following:

- Positive bone scan

- Palpable disease

- The following positive imaging studies:

- Two consecutively rising PSA levels taken at least 1 week apart, with 1 level that is

50% above the nadir reached after the last therapeutic maneuver (as long as the last measurement is at least 5 ng/mL)

- At least 1 lesion consistent with metastatic cancer on technetium Tc 99m whole body

scintigraphy AND/OR

- Soft-tissue metastases as measured by appropriate modalities (i. e., imaging and

palpation)

- HLA-A2 positive (phase II only)

- No brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- More than 6 months

Hematopoietic

- Granulocyte count at least 1,500/mm^3

- Platelet count at least 100,000/mm^3

- Lymphocyte count at least 500/mm^3

- Hemoglobin at least 10 g/dL

Hepatic

- Bilirubin less than 1. 5 mg/dL

- AST and ALT less than 2. 5 times upper limit of normal

- Hepatitis B negative

- Hepatitis C negative

Renal

- Creatinine clearance greater than 60 mL/min

- Creatinine normal

- No proteinuria 1,000 mg or greater by 24-hour urine collection

- No hematuria*

- No abnormal sediment* NOTE: *Patient may be eligible provided the underlying cause is

determined to be non-renal

Cardiovascular

- No prior unstable or newly diagnosed angina pectoris

- No myocardial infarction within the past 6 months

- No New York Heart Association class II-IV congestive heart failure

- No clinically significant cardiomyopathy requiring treatment

Immunologic

- HIV negative

- No active infection within the past 3 days

- No allergy or untoward reaction to prior vaccinia virus vaccination

- No concurrent significant autoimmune disease that is active or potentially

life-threatening if activated

- No known allergy to eggs

Other

- Fertile patients must use effective contraception

- No other active malignancy within the past 2 years except nonmelanoma skin cancer or

carcinoma in situ of the bladder

- No other concurrent serious or life-threatening illness

- No eczema or eczematoid skin disorders

- No acute, chronic, or exfoliative skin conditions, including:

- Atopic dermatitis

- Burns

- Impetigo

- Varicella zoster

- Severe acne

- Other open rashes or wounds

- No close household contact with persons meeting any of the following criteria for at

least 3 weeks after vaccination:

- Prior or active eczema or other eczematoid skin disorders

- Acute, chronic, or exfoliative skin conditions (e. g., atopic dermatitis, burns,

impetigo, varicella zoster, severe acne, or other open rashes or wounds)

- Pregnant or nursing women

- Children under 5 years of age

- Immunodeficient or immunosuppressed (including HIV infection) individuals

- Willing and able to travel to the National Institutes of Health for follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior PSA vaccine therapy (phase II only)

Chemotherapy

- More than 3 years since prior therapy with any of the following (phase II only):

- Docetaxel

- Paclitaxel

- Doxorubicin

- Cisplatin

- Carboplatin

- Mitoxantrone

- Estramustine

- Cyclophosphamide

- Irinotecan

- Topotecan

Endocrine therapy

- See Disease Characteristics

- No concurrent steroid therapy (except topical or inhaled steroids)

- Patients concurrently receiving luteinizing hormone-releasing factor analog therapy

must continue therapy during study participation

Radiotherapy

- At least 4 weeks since prior radiotherapy

Surgery

- No prior splenectomy

Other

- Recovered from all prior therapy

- No concurrent antibiotics

- No other concurrent antitumor therapy

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda, Maryland 20892-1182, United States; Recruiting
Patient Recruitment, Phone: 888-NCI-1937

Clinical trial summary from the National Cancer Institute's PDQ® database

Featured trial article

Related publications:

Arlen PM, Gulley J, Dahut W, et al.: A phase I study of sequential vaccinations with recombinant Fowlpox-PSA (L155)-TRICOM (rF) alone, or in combination with recombinant vaccinia-PSA (L155)-TRICOM (rV), and the role of GM-CSF, in patients (Pts) with prostate cancer. [Abstract] J Clin Oncol 22 (Suppl 14): A-2522, 168s, 2004.

Last updated: April 5, 2006