Vaccine Therapy, MDX-010, and GM-CSF in Treating Patients With Metastatic Prostate Cancer

Condition(s) targeted: Prostate Cancer

Intervention: fowlpox-PSA-TRICOM vaccine (Drug); ipilimumab (Drug); sargramostim (Drug); vaccinia-PSA-TRICOM vaccine (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
James Gulley, MD, PhD, Principal Investigator, Affiliation: National Cancer Institute (NCI)

RATIONALE: Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Biological therapies, such as MDX-010 and GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. Giving vaccine therapy together with MDX-010 and GM-CSF may be an effective treatment for prostate cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of MDX-010 when given together with vaccine therapy and GM-CSF in treating patients with metastatic prostate cancer.

Official title: Phase I Trial of a PSA Based Vaccine and an Anti-CTLA-4 Antibody in Adults With Metastatic Androgen Independent Prostate Cancer

Study design: Treatment, Open Label

Primary outcome: Safety by CTCAE v 3.0

Secondary outcome:

Objective responses by RECIST every 2 months

Prostate-specific antigen (PSA) response by monthly serum PSA

Compare immunologic responses by ELISPOT at baseline and day 99

Detailed description: OBJECTIVES:

Primary

- Determine the maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4

monoclonal antibody (MDX-010) when given with sargramostim (GM-CSF) and vaccine therapy comprising vaccinia-PSA-TRICOM vaccine and fowlpox-PSA-TRICOM vaccine in patients with androgen-independent metastatic prostate cancer.

- Determine the safety and tolerability of this regimen in these patients.

Secondary

- Determine immunologic response, as measured by an increase in prostate-specific antigen

(PSA) specific T-cells by ELISPOT assay, in HLA-A2-positive patients treated with this regimen.

- Determine the clinical response, as measured by RECIST and PSA consensus criteria, in

patients treated with this regimen.

OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010).

Patients receive a priming vaccination with vaccinia-PSA-TRICOM vaccine subcutaneously (SC) on day 1 and sargramostim (GM-CSF) SC on days 1-4. Patients then receive booster vaccinations with fowlpox-PSA-TRICOM vaccine SC and MDX-010 IV over 90 minutes on days 15, 43, 71, 99, 127, and 155. Patients also receive GM-CSF SC on days 15-18, 43-46, 71-74, 99-102, 127-130, and 155-158. Patients without disease progression after day 155 may continue to receive fowlpox-PSA-TRICOM vaccine and GM-CSF every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of MDX-010 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

After completion of study treatment, patients are followed at 4 weeks and then annually for 15 years.

PROJECTED ACCRUAL: A maximum of 30 patients will be accrued for this study within 2-3 years.

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

Criteria:

DISEASE CHARACTERISTICS:

- Histologically confirmed prostate cancer

- Metastatic disease

- Androgen-independent disease

- No bone pain requiring narcotics

- No brain metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-1

Life expectancy

- At least 6 months

Hematopoietic

- Granulocyte count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Lymphocyte count ≥ 500/mm^3

- Hemoglobin ≥ 9 g/dL

Hepatic

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

- Bilirubin ≤ 1. 5 mg/dL (total bilirubin ≤ 3. 0 mg/dL for patients with Gilbert's

syndrome)

- Hepatitis B negative

- Hepatitis C negative

Renal

- Creatinine clearance ≥ 60 mL/min

- No proteinuria ≥ grade 2 (unless the cause is determined to be nonrenal)

Cardiovascular

- No history of congestive heart failure OR objective evidence of congestive heart

failure by physical exam or imaging

- No New York Heart Association class II-IV cardiac disease

Pulmonary

- No pulmonary disease with fatigue or dyspnea during ordinary physical activity

Gastrointestinal

- No inflammatory bowel disease

- No Crohn's disease

- No ulcerative colitis

- No active diverticulitis

Immunologic

- HIV negative

- No history of allergy or untoward reaction to prior vaccination with vaccinia virus or

to any component of the vaccinia regimen

- No serious hypersensitivity reaction to egg products

- No autoimmune disease that requires treatment, including any of the following:

- Addison's disease

- Hashimoto's thyroiditis

- Systemic lupus erythematosus

- Sjögren's syndrome

- Scleroderma

- Myasthenia gravis

- Goodpasture's syndrome

- Active Graves disease

- History of autoimmunity allowed provided it has not required systemic

immunosuppressive therapy OR does not threaten vital organ function, including the CNS, heart, lungs, kidneys, skin, and gastrointestinal tract

- No history of multiple sclerosis

- No immunodeficiency or immunosuppression (by disease or therapy)

- No history of or active eczema or other eczematoid skin disorder

- No other acute, chronic, or exfoliative skin condition, including any of the

following:

- Atopic dermatitis

- Burns

- Impetigo

- Varicella zoster

- Severe acne

- Other open rashes or wounds

Other

- Fertile patients must use effective contraception during and for ≥ 4 months after

completion of study treatment

- No history of seizures

- No history of encephalitis

- No other active malignancy within the past 12 months except nonmelanoma skin cancer or

carcinoma in situ of the bladder

- No life-threatening illness

- Able to avoid close household contact with the following individuals for ≥ 3 weeks

after vaccination:

- Individuals with prior or active eczema or other eczematoid skin disorder

- Individuals with other acute, chronic, or exfoliative skin condition, including

any of the following:

- Atopic dermatitis

- Burns

- Impetigo

- Varicella zoster

- Severe acne

- Other open rashes or wounds

- Children 3 years of age or younger

- Pregnant or nursing women

- Immunodeficient or immunosuppressed individuals (by disease or therapy),

including HIV-infected individuals

- No other serious medical illness that requires treatment and would preclude study

participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Prior vaccinia immunization allowed

- No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

(MDX-010)

- No other concurrent anticancer immunotherapy

Chemotherapy

- See Disease Characteristics

- No prior chemotherapy

- No concurrent chemotherapy

Endocrine therapy

- More than 2 weeks since prior and no concurrent systemic or topical steroids,

including steroid eye drops

- Nasal or inhaled steroids allowed

- Concurrent gonadotropin-releasing hormone agonist or antagonist therapy required for

patients who have not undergone prior bilateral surgical orchiectomy

- No concurrent anticancer systemic glucocorticoids

- Concurrent replacement glucosteroids for patients with pituitary insufficiency

allowed

- Concurrent steroids for therapy-induced autoimmunity allowed

Radiotherapy

- No concurrent anticancer radiotherapy

Surgery

- See Endocrine therapy

- Recovered from prior surgery

- No prior splenectomy

- No concurrent major surgery for treatment of cancer

Other

- Recovered from prior therapy

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office, Bethesda, Maryland 20892-1182, United States; Recruiting
Clinical Trials Office - Warren Grant Magnusen Clinical Center, Phone: 888-NCI-1937

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

Web site for additional information

Starting date: June 2005
Last updated: June 12, 2008