Biological Therapy in Treating Patients With Metastatic Cancer

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004604
• Other study ID #: CDR0000065619
• Secondary ID: 1817
• Status: Completed
• Phase: Phase 1
• First received: May 2, 2000
• Last updated: February 21, 2013
• Start date: February 1997
• Est. completion date: July 2002

Study information

• Verified date: February 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2002
• Est. primary completion date: June 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Bile Duct Neoplasms
• Breast Cancer
• Cholangiocarcinoma
• Colorectal Cancer
• Extrahepatic Bile Duct Cancer
• Gallbladder Cancer
• Gallbladder Neoplasms
• Gastric Cancer
• Head and Neck Cancer
• Head and Neck Neoplasms
• Liver Cancer
• Lung Cancer
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Neoplasms, Second Primary
• Ovarian Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms
• Stomach Neoplasms
• Testicular Germ Cell Tumor
• Testicular Neoplasms

Intervention

Biological:
• CEA RNA-pulsed DC cancer vaccine
carcinoembryonic antigen RNA-pulsed dendritic cells

Locations

Country	Name	City	State
United States	Duke Comprehensive Cancer Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	To determine the safety and dose limiting toxicity of intravenous injections of autologous, cultured, dendritic cells pulsed with CEA RNA.	12 months	Yes
Secondary	Immune response	Evaluation of cellular immune response to the CEA protein. Evaluation of clinical and biochemical response to the treatment and the duration of such response	12 weeks	No