Clinical trial NCT00010127: Vaccine Therapy in Treating Patients With Metastatic Prostate Cancer
Official title: A Safety and Feasibility Study of Active Immunotherapy in Patients With Metastatic Prostate Carcinoma Using Autologous Dendritic Cells Pulsed With Antigen Encoded in Amplified Autologous Tumor RNA
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IV prostate cancer
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-07-30
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from a person's cancer cells may make the body build an immune response to kill prostate tumor cells.

PURPOSE: Phase I trial to study the effectiveness of vaccine therapy in treating patients who have metastatic prostate cancer.

Detailed description: OBJECTIVES:

* Determine the safety and feasibility of autologous dendritic cells transfected with autologous total tumor RNA in patients with metastatic prostate cancer.
* Determine the presence, frequency, and activation status of tumor specific and prostate specific antigen (PSA) specific cellular immune responses in patients treated with this regimen.
* Determine delayed-type hypersensitivity reactions to PSA protein and other recall antigens in patients before and after being treated with this regimen.
* Determine clinical responses based on clinical and biochemical (PSA) response criteria in patients treated with this regimen.
* Determine a platform for immunological treatment using dendritic-cell based tumor vaccines in these patients.

OUTLINE: This is a dose escalation study.

Tumor tissue and peripheral blood stem cells are collected from patients and cultured in vitro with sargramostim (GM-CSF) and interleukin-4 for 7 days to produce dendritic cells (DC). Patients receive autologous DC transfected with autologous prostate carcinoma RNA intradermally once weekly on weeks 0-3 for a total of 4 doses.

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

Patients are followed at weeks 6, 8, 10, and 12; every 3 months for 9 months; and then annually for 2 years.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study within 20 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed metastatic adenocarcinoma of the prostate

  * Stage D1-3
  * Regional lymph node, bone, visceral, or soft tissue metastases
  * No transitional cell or small cell carcinoma
* Testosterone less than 50 mg/L if prior treatment with luteinizing hormone releasing hormone (LHRH) analogues or estrogens
* Evidence of androgen refractory disease after surgical castration and discontinuation of LHRH analogue therapy
* No previously irradiated or new CNS metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 70-100%

Life expectancy:

* More than 6 months

Hematopoietic:

* WBC at least 3,000/mm\^3
* Hemoglobin at least 9 g/dL
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin less than 2.0 mg/dL
* PT at least 11.3 seconds but no greater than 13.3 seconds
* PTT at least 20.1 seconds but no greater than 32.9 seconds
* No hepatic disease
* No viral hepatitis

Renal:

* Creatinine less than 2.5 mg/dL

Cardiovascular:

* No New York Heart Association class III or IV heart disease

Pulmonary:

* No asthma
* No chronic obstructive pulmonary disease
* No severe lung disease

Other:

* No other medical illness or psychological impediment that would preclude study
* No other concurrent malignancy except nonmelanoma skin cancer or controlled superficial bladder cancer
* No active acute or chronic infection including symptomatic urinary tract infection
* No autoimmune disease (e.g., inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, scleroderma, or multiple sclerosis)
* HIV negative
* Adequate peripheral vein access

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Prior biologic therapy allowed
* No other concurrent immunotherapy

Chemotherapy:

* Prior chemotherapy allowed
* No concurrent chemotherapy

Endocrine therapy:

* See Disease Characteristics
* At least 4 weeks since prior non-steroidal hormonal therapy if increase in PSA while receiving non-steroidal hormonal therapy
* At least 6 weeks since prior steroids
* Concurrent LHRH analogues for gonadal androgen suppression allowed
* No concurrent steroid therapy
* No concurrent corticosteroids

Radiotherapy:

* See Disease Characteristics
* Prior palliative radiotherapy for bone metastases allowed
* Prior prostatic radiotherapy allowed
* At least 4 weeks since prior radiotherapy
* At least 12 weeks since prior strontium chloride Sr 89
* No concurrent radiotherapy

Surgery:

* See Disease Characteristics

Other:

* Recovered from prior therapy
* No concurrent immunosuppressive agents (e.g., azathioprine or cyclosporine)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: Johannes Vieweg, MD
role: STUDY_CHAIR
References: