Vaccine Therapy in Treating Patients With Refractory Stage IV Cancer

Duke University

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Biological: CEA peptide 1-6D

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00057915

4180 (Other Identifier)

5910 (Other Grant/Funding Number)

Details and patient eligibility

About

RATIONALE: Vaccines made from a person's white blood cells mixed with peptides may make the body build an immune response to kill cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with refractory stage IV cancer.

Full description

OBJECTIVES:

• 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.
• Determine the ability of this regimen to induce CAP 1-6D- and CMV pp65-specific T cells in these patients.
• Determine the antitumor effect of this regimen, in terms of progression-free survival, of these patients.

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.

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

Enrollment: 4 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 6 months

Hematopoietic

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

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

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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4 participants in 1 patient group

CEA peptide 1-6D

Experimental group

Description:

CAP-1(6D) peptide-pulsed, matured, autologous human DC produced by the AastromReplicell™ Cell Production System

Treatment:

Biological: CEA peptide 1-6D