Clinical trial NCT00027534: Vaccine Therapy in Treating Patients With Advanced or Metastatic Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Colorectal Cancer
Gallbladder Cancer
Gastric Cancer
Head and Neck Cancer
Liver Cancer
Ovarian Cancer
Pancreatic Cancer
Testicular Germ Cell Tumor
Keywords: recurrent colon cancer
stage III colon cancer
stage IV colon cancer
recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent gastric cancer
stage III gastric cancer
stage IV gastric cancer
recurrent pancreatic cancer
stage II pancreatic cancer
stage III pancreatic cancer
recurrent rectal cancer
stage III rectal cancer
stage IV rectal cancer
advanced adult primary liver cancer
recurrent adult primary liver cancer
recurrent gallbladder cancer
unresectable gallbladder cancer
thyroid gland medullary carcinoma
recurrent salivary gland cancer
stage III salivary gland cancer
stage IV salivary gland cancer
Paget disease of the breast with intraductal carcinoma
Paget disease of the breast with invasive ductal carcinoma
adult primary hepatocellular carcinoma
diffuse adenocarcinoma of the stomach
intestinal adenocarcinoma of the stomach
mixed adenocarcinoma of the stomach
adenocarcinoma of the colon
adenocarcinoma of the gallbladder
adenocarcinoma of the rectum
recurrent malignant testicular germ cell tumor
stage II malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
male breast cancer
adenocarcinoma of the pancreas
cholangiocarcinoma of the gallbladder
salivary gland adenocarcinoma
ovarian endometrioid adenocarcinoma
stage IV pancreatic cancer
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Safety
timeFrame: 12-36 weeks
Secondary outcomes:
measure: Immune response
timeFrame: 12-36 weeks
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Duke Cancer Institute
name: Herbert K. Lyerly, MD
role: STUDY_CHAIR
References: