RATIONALE: Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic cancer that has not responded to previous treatment.

Condition	Treatment or Intervention	Phase
Lung Cancer Testicular Cancer ovarian epithelial cancer Pancreatic Cancer Colon Cancer Thyroid Cancer Gastric Cancer Salivary Gland Cancer Rectal Cancer Breast Cancer Head and Neck Cancer Colorectal Cancer adult primary liver cancer	Drug: carcinoembryonic antigen RNA-pulsed DC cancer vaccine	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and dose limiting toxicity of an intravenous vaccine of autologous, cultured, dendritic cells pulsed with carcinoembryonic antigen (CEA) RNA in patients with metastatic adenocarcinoma expressing CEA. II. Assess the cellular immune response to the CEA protein. III. Assess the clinical and biochemical response to the treatment and the duration of such response.

PROTOCOL OUTLINE: This a three tiered, open label, uncontrolled, dose escalation study. The first 3 patients receive a low dose of intravenous carcinoembryonic antigen (CEA) RNA-pulsed autologous dendritic cells (DC) at weeks 0, 1, 2, and 3. Patients are evaluated for dose limiting toxicity (DLT), immune response, and the antitumor response for at least 1 week before dose escalation may proceed. If there is no DLT in the first three, the next 3 patients are treated at a medium dose of CEA RNA-pulsed autologous DC at 0, 1, 2, and 3 weeks. Finally, if DLT is not seen at the medium dose, the final 6 patients receive intravenous infusions of a high dose of CEA RNA-pulsed autologous DC at weeks 0, 1, 2, and 3. If 1-2 patient(s) experience DLT at the either the low or medium dose levels, 3 more patients are entered at the same dose. If no further DLT occurs, then dose escalation continues. As soon as 3 toxic events occur in 3-6 patients at one dose level, accrual at that level ceases. The MTD is defined as the dose level immediately below that at which more than 3 of 6 patients develop DLT.

PROJECTED ACCRUAL: A minimum of 3 and a maximum of 18 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed metastatic adenocarcinoma expressing carcinoembryonic antigen (CEA) that has failed conventional therapy
• Measurable or evaluable disease; May include elevated CEA level
• No previously irradiated or known new CNS metastases

--Prior/Concurrent Therapy--

• Must have recovered from all acute toxic effects
• Biologic therapy: No concurrent biologic therapy; At least 6 weeks since biologic therapy; No concurrent immunotherapy No more than 1 prior biologic regimen
• Chemotherapy: No concurrent chemotherapy; At least 6 weeks since chemotherapy; No more than 1 prior chemotherapy regimen
• Endocrine therapy: At least 6 weeks since steroid therapy
• Radiotherapy: No concurrent radiotherapy; At least 12 weeks since therapy including Sr 89; At least 6 weeks since other radiotherapy; No prior cranial radiotherapy
• Surgery: Not specified
• Other: No concurrent immunosuppressives such as azathioprine or cyclosporine

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: Greater than 6 months
• Hematopoietic: WBC at least 3,000/mm3; Absolute lymphocyte count at least 1,000/mm3; Hemoglobin at least 9 g/dL; Platelet count at least 100,000/mm3; PT less than 1.25 times normal limit; PTT less that 1.66 times normal limit; Fibrinogen greater than 0.75 times normal limit
• Hepatic: Bilirubin less than 2.0 mg/dL
• Renal: Creatinine less than 2.5 mg/dL
• Cardiovascular: No NYHA class III or IV
• Pulmonary: FEV1 greater than 70% of predicted; FVC greater than 70% of predicted DLCO greater than 70% of predicted; No asthma or chronic obstructive pulmonary disease
• Other: No active or chronic infection (including urinary tract infection); No viral hepatitis; HIV negative; No concurrent second malignancy other than nonmelanoma skin cancer or controlled superficial bladder cancer; No hepatic disease; No history of other autoimmune disease such as inflammatory bowel disease, systemic lupus erythematous, ankylosing spondylitis, scleroderma, or multiple sclerosis

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States

Study chairs or principal investigators

Herbert Kim Lyerly,  Study Chair,  Duke Comprehensive Cancer Center   

Study ID Numbers:  CDR0000065619; DUMC-96098; NCI-G97-1272; DUMC-1817-99-10R3
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  May 2, 2000
ClinicalTrials.gov Identifier:  NCT00004604
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08