Vaccine Therapy in Treating Patients With Advanced or Metastatic Cancer

Michael Morse, MD

Status and phase

Completed

Phase 1

Conditions

Gallbladder Cancer

Breast Cancer

Gastric Cancer

Ovarian Cancer

Head and Neck Cancer

Liver Cancer

Testicular Germ Cell Tumor

Pancreatic Cancer

Colorectal Cancer

Treatments

Biological: TRICOM-CEA(6D)

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00027534

2840 (Other Identifier)

1R21CA094523 (U.S. NIH Grant/Contract)

CDR0000069041

Details and patient eligibility

About

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.

Full 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.

Enrollment

14 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)