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A Phase I Study of Active Immunotherapy With Carcinoembryonic Antigen RNA-Pulsed, Autologous Human Cultured Dendritic Cells in Patients With Metastatic Malignancies Expressing Carcinoembryonic Antigen


Phase 1
18 Years
N/A
Not Enrolling
Both
Breast Cancer, Colorectal Cancer, Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Gastric Cancer, Head and Neck Cancer, Liver Cancer, Lung Cancer, Metastatic Cancer, Ovarian Cancer, Pancreatic Cancer, Testicular Germ Cell Tumor

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Trial Information

A Phase I Study of Active Immunotherapy With Carcinoembryonic Antigen RNA-Pulsed, Autologous Human Cultured Dendritic Cells in Patients With Metastatic Malignancies Expressing Carcinoembryonic Antigen


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.

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.

Inclusion 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

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

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety

Outcome Description:

To determine the safety and dose limiting toxicity of intravenous injections of autologous, cultured, dendritic cells pulsed with CEA RNA.

Outcome Time Frame:

12 months

Safety Issue:

Yes

Principal Investigator

Herbert K. Lyerly, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Duke Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000065619

NCT ID:

NCT00004604

Start Date:

February 1997

Completion Date:

July 2002

Related Keywords:

  • Breast Cancer
  • Colorectal Cancer
  • Extrahepatic Bile Duct Cancer
  • Gallbladder Cancer
  • Gastric Cancer
  • Head and Neck Cancer
  • Liver Cancer
  • Lung Cancer
  • Metastatic Cancer
  • Ovarian Cancer
  • Pancreatic Cancer
  • Testicular Germ Cell Tumor
  • stage IV colon cancer
  • stage IV breast cancer
  • recurrent breast cancer
  • stage IV gastric cancer
  • recurrent gastric cancer
  • recurrent non-small cell lung cancer
  • recurrent pancreatic cancer
  • stage IV rectal cancer
  • recurrent colon cancer
  • recurrent rectal cancer
  • inflammatory breast cancer
  • stage IV ovarian epithelial cancer
  • recurrent ovarian epithelial cancer
  • extensive stage small cell lung cancer
  • recurrent small cell lung cancer
  • unresectable gallbladder cancer
  • recurrent gallbladder cancer
  • unresectable extrahepatic bile duct cancer
  • recurrent extrahepatic bile duct cancer
  • stage III malignant testicular germ cell tumor
  • recurrent malignant testicular germ cell tumor
  • thyroid gland medullary carcinoma
  • stage IV non-small cell lung cancer
  • stage IV salivary gland cancer
  • recurrent salivary gland cancer
  • Paget disease of the breast with invasive ductal carcinoma
  • adult primary hepatocellular carcinoma
  • testicular yolk sac tumor
  • lung metastases
  • liver metastases
  • cholangiocarcinoma of the gallbladder
  • cholangiocarcinoma of the extrahepatic bile duct
  • male breast cancer
  • stage IV pancreatic cancer
  • Breast Neoplasms
  • Colorectal Neoplasms
  • Head and Neck Neoplasms
  • Liver Neoplasms
  • Lung Neoplasms
  • Stomach Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Ovarian Neoplasms
  • Pancreatic Neoplasms
  • Gallbladder Neoplasms
  • Bile Duct Neoplasms
  • Neoplasms, Germ Cell and Embryonal

Name

Location
Duke Comprehensive Cancer Center Durham, North Carolina  27710