Vaccine Therapy in Treating Patients With Advanced or Metastatic Cancer

Sponsor

Michael Morse, MD (Other)

Overall Status

Completed

CT.gov ID

NCT00027534

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from a person's white blood cells that have been treated in the laboratory may make the body build an immune response to kill tumor cells.

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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Colorectal Cancer Gallbladder Cancer Gastric Cancer Head and Neck Cancer Liver Cancer Ovarian Cancer Pancreatic Cancer Testicular Germ Cell Tumor	Biological: TRICOM-CEA(6D)	Phase 1

Detailed Description

OBJECTIVES:

Determine the safety and feasibility of active immunotherapy comprising autologous dendritic cells infected with recombinant fowlpox-CEA-TRICOM vaccine in patients with advanced or metastatic malignancies expressing CEA.
Assess the CEA-specific immune response of patients treated with this regimen.
Assess, in a preliminary manner, the clinical response rate of patients treated with this regimen.

OUTLINE: This is a dose-escalation study.

Autologous dendritic cells (ADCs) are harvested and infected with fowlpox-CEA-TRICOM vaccine. Patients receive the infected ADCs intradermally and subcutaneously (SC) followed by ADCs mixed with CMV pp65 peptide and ADCs mixed with tetanus toxoid SC and intradermally on day 1. Treatment repeats every 3 weeks for a total of 4, 8, or 12 immunizations in the absence of unacceptable toxicity.

Cohorts of 6 patients receive an escalating number of immunizations 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.

Patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study Of Active Immunotherapy With Autologous Dendritic Cells Infected With CEA-6D Expressing Fowlpox -Tricom In Patients With Advanced Or Metastatic Malignancies Expressing CEA

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Oct 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TRICOM-CEA(6D) Subjects receiving TRICOM-CEA(6D)	Biological: TRICOM-CEA(6D) dendritic cells loaded with TRICOM-CEA(6D) Other Names: recombinant fowlpox-CEA(6D)/TRICOM vaccine

Arm

Intervention/Treatment

Experimental: TRICOM-CEA(6D)

Subjects receiving TRICOM-CEA(6D)

Biological: TRICOM-CEA(6D)

dendritic cells loaded with TRICOM-CEA(6D)

Other Names:

recombinant fowlpox-CEA(6D)/TRICOM vaccine

Outcome Measures

Primary Outcome Measures

Safety [12-36 weeks]
The primary objective of this protocol is to determine the safety and feasibility of rF-CEA(6D)-TRICOM loaded DC in, subjects with metastatic, CEA expressing malignancies.

Secondary Outcome Measures

Immune response [12-36 weeks]
The immune response to the injections of the TRICOM-CEA(6D) antigen loaded DC will be evaluated

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed advanced or metastatic malignancy expressing CEA
Metastatic disease meeting one of the following criteria:
Measurable or nonmeasurable
History of metastases but no current evidence of disease, meeting one of the following criteria:
Unresectable peritoneal or lymph node metastases that cannot be detected by imaging
Treated or resected metastatic disease considered at high risk of recurrence (predicted 5-year disease-free survival of less than 50%)
Must have completed treatment that rendered no evidence of disease within the past year
CEA-expressing malignancy is defined by any of the following:
Immunohistochemical staining (at least 50% of the tumor has at least a moderate intensity of staining)
CEA level in peripheral blood greater than 2.5 µg/L
Tumor known to be universally CEA positive (e.g., colon and rectal cancer)
Received prior therapy with possible survival benefit or refused such therapy
Prior resection of brain metastases allowed provided no metastasis by CT scan or MRI of the brain within 1 month of enrollment
Hormone receptor status:
Not specified

PATIENT CHARACTERISTICS:

Age

18 and over Sex
Male or female Menopausal status
Not specified Performance status
Karnofsky 70-100% Life expectancy
More than 6 months

Hematopoietic

WBC at least 3,000/mm^3
Absolute lymphocyte count at least 1,000/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 9 g/dL (transfusion or epoetin alfa allowed) Hepatic
Bilirubin less than 2.0 mg/dL
SGOT/SGPT less than 1.5 times upper limit of normal
No active acute or chronic viral hepatitis
Hepatitis B surface antigen negative
Hepatitis C negative
No other hepatic disease that would preclude study entry

Renal

Creatinine less than 2.5 mg/dL
No active acute or chronic urinary tract infection

Cardiovascular

No New York Heart Association class III or IV heart disease Immunologic
HIV negative
No history of autoimmune disease, including, but not limited to, the following:
Inflammatory bowel disease
Systemic lupus erythematosus
Rheumatoid arthritis
Ankylosing spondylitis
Scleroderma
Multiple sclerosis
No allergy to eggs or any component of study vaccine Other
No active acute or chronic infection
No concurrent serious acute or chronic illness that would preclude study entry
No other medical or psychological impediment that would preclude study entry
No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 4 weeks since prior biologic therapy and recovered
No other concurrent immunotherapy

Chemotherapy

At least 4 weeks since prior chemotherapy and recovered
No concurrent chemotherapy

Endocrine therapy

At least 4 weeks since prior hormonal therapy and recovered
At least 6 weeks since prior steroids except steroids used as premedication for chemotherapy or for contrast-enhanced studies
No concurrent steroids

Radiotherapy

Prior palliative radiotherapy (including systemic radiolabeled compounds) for unstable or painful bone metastases in weight-bearing bones may be allowed
At least 4 weeks since prior radiotherapy and recovered
No concurrent radiotherapy

Surgery

Not specified

Other

At least 4 weeks since any other prior therapy (including experimental therapy) and recovered
No concurrent immunosuppressives (e.g., azathioprine or cyclosporine)