Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy in Treating Patients With Refractory Stage IV Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 and over	NCI	DUMC-4180-03-10R1 NCI-5910, NCT00057915, 5910

Objectives

1. Determine the safety and feasibility of administering 1 or 2 courses of vaccination with carcinoembryonic antigen peptide 1-6D (CAP 1-6D)- and CMV pp65 peptide-pulsed autologous dendritic cells in patients with refractory stage IV CEA-expressing malignancies.
2. Determine the ability of this regimen to induce CAP 1-6D- and CMV pp65-specific T cells in these patients.
3. Determine the antitumor effect of this regimen, in terms of progression-free survival, of these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed malignancy that is refractory to standard therapy known to have a survival benefit
  • Stage IV disease



• Carcinoembryonic antigen (CEA)-expressing tumor, as evidenced by 1 of the following:
  • Immunohistochemistry with at least 50% of the tumor with at least moderate intensity of staining
  • Peripheral blood CEA greater than 2.5 mg/dL
  • Tumor known to be universally CEA positive (i.e., colon or rectal cancer)



• HLA-A201 positive



• Measurable disease*
  • At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

   [Note: *Histologic or cytologic confirmation is not required for measurable disease restricted to a solitary lesion]




• Received at least 1 prior standard chemotherapy regimen known to have a survival benefit



• Previously resected brain metastases allowed provided CT scan or MRI was performed within the past month and shows no metastasis

Prior/Concurrent Therapy:

Biologic therapy

• At least 4 weeks since prior immunotherapy
• No other concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy

• At least 6 weeks since prior steroid therapy (except steroids administered as premedication for chemotherapy or contrast-enhanced studies)
• Concurrent hormonal therapy allowed for patients with breast cancer
• No concurrent steroid therapy

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• Recovered from prior therapy
• At least 4 weeks since prior investigational therapy
• At least 4 weeks since other prior therapy
• Any number of prior therapies are allowed
• Concurrent bisphosphonates allowed for bone metastases
• No concurrent immunosuppressive therapy (e.g., azathioprine or cyclosporine)
• No other concurrent experimental therapies

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 6 months

Hematopoietic

• WBC at least 3,000/mm³
• Hemoglobin at least 9 g/dL (transfusions or red blood cell growth factors [e.g., epoetin alfa] allowed)
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin less than 2.0 mg/dL (unless patient has Gilbert's disease)
• SGOT/SGPT less than 1.5 times upper limit of normal
• No hepatic disease that would preclude study participation
• No viral hepatitis (including chronic hepatitis) by hepatitis B surface antigen and hepatitis C serology

Renal

• Creatinine less than 2.5 mg/dL
• No urinary tract infection

Cardiovascular

• No New York Heart Association class III or IV heart disease

Immunologic

• No history of autoimmune disease, including any of the following:
  • Inflammatory bowel disease
  • Systemic lupus erythematosus
  • Ankylosing spondylitis
  • Scleroderma
  • Multiple sclerosis
• No active acute or chronic infection
• HIV negative

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other serious chronic or acute illness that would preclude study participation
• No medical or psychological impediment that would preclude study compliance
• No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer
• No allergy to study vaccine components

Expected Enrollment

A total of 12 patients (6 per cohort) will be accrued for this study within 24 months.

Outline

This is an open-label, dose-escalation study.

Patients undergo leukapheresis and collection of peripheral blood mononuclear cells from which dendritic cells (DC) are generated and pulsed with carcinoembryonic antigen peptide 1-6D (CAP 1-6D) and CMV pp65 peptide. Patients are assigned to 1 of 2 vaccination cohorts.

• Cohort I: Patients receive vaccination with CAP 1-6D-pulsed DC and CMV pp65 peptide-pulsed DC subcutaneously and intradermally every 3 weeks for a total of 4 vaccinations.



• Cohort II: Patients receive vaccinations as in cohort I every 3 weeks for a total of 8 vaccinations.

For both cohorts, a safe dose of the vaccine is defined as the dose at which no more than 1 of 6 patients experiences unacceptable toxicity.

Patients are followed every 3 months for 1 year.

Trial Contact Information

Trial Lead Organizations

Duke Comprehensive Cancer Center

Herbert Lyerly, MD, Protocol chair		Ph: 919-684-5613

Registry Information
Official Title		A Phase I Study of Active Immunotherapy with CAP-1 (6D) and CMVpp65 Peptide-Pulsed, Autologous Dendritic Cells Produced in the Aastromreplicell Cell Production System in Patients with Stage IV CEA Expressing Malignancies
Trial Start Date		2003-09-04
Registered in ClinicalTrials.gov		NCT00057915
Date Submitted to PDQ		2003-02-04
Information Last Verified		2006-09-13
NCI Grant/Contract Number		CA14236

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