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

Alternate Title

Vaccine Therapy and Radiation Therapy in Treating Patients With Carcinoembryonic Antigen-Positive Solid Tumors That Have Metastasized to the Liver

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
No phase specified	Treatment	Closed	18 and over	NCI	NCI-04-C-0167 6368, NCI-6368, NCT00085241

Objectives

Primary

1. Determine the clinical safety of vaccinia-CEA-TRICOM vaccine, fowlpox-CEA-TRICOM vaccine, recombinant fowlpox GM-CSF vaccine, and radiotherapy in patients with carcinoembryonic antigen (CEA)-positive solid tumors metastatic to the liver.

Secondary

1. Determine the clinical response in patients receiving this regimen.
2. Determine the immunological response, specifically the CEA-specific T-cell response, in patients receiving this regimen.
3. Determine the effect of radiotherapy (before and after treatment) on FAS, major histocompatability complex, p53, and CEA in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of solid tumor
  • Radiographically visible metastatic liver lesions that are life-threatening
  • Carcinoembryonic antigen (CEA)-positive disease that meets one of the following criteria:
    • ≥ 20% of cells stained immunohistochemically
    • Elevated serum CEA (> 5 ng/mL) at any time during disease course



• Received at least 1 prior chemotherapy regimen for metastatic disease



• Vaccinia-naïve OR vaccinia-immune



• No known brain metastases

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• Prior immunotherapy allowed
• No other concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No concurrent chemotherapy

Endocrine therapy

• No concurrent systemic steroids except physiologic doses for systemic steroid replacement or local (topical, nasal, or inhaled) steroids
• At least 2 weeks since prior steroid eye drops
• No concurrent steroid eye drops during and for 4 weeks after vaccinia vaccination
• No concurrent hormone therapy
• No concurrent dexamethasone or other steroid as an antiemetic

Radiotherapy

• No prior radiotherapy to > 50% of all nodal groups
• No prior radiotherapy to the whole liver
• No other concurrent radiotherapy

Surgery

• No prior splenectomy
• No concurrent major surgery

Other

• Recovered from all prior therapy
• At least 4 weeks since prior cytotoxic therapy
• No concurrent aprepitant
• No other concurrent anticancer therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 6 months

Hematopoietic

• Granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8 g/dL
• Absolute lymphocyte count ≥ 400/mm³

Hepatic

• See Disease Characteristics
• AST ≤ 2 times upper limit of normal
• Bilirubin normal (≤ 3 times ULN with Gilbert's syndrome)
• PT and PTT normal
• Hepatitis B and C negative
• No chronic liver disease, including the following:
  • End stage cirrhosis
  • Chronic active hepatitis by surface antigen or core antibody test

Renal

• Creatinine normal

  OR

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No New York Heart Association class II-IV heart disease
• No evidence of congestive heart failure by physical exam or imaging
• No clinically significant cardiomyopathy requiring treatment

Pulmonary

• No pulmonary disease with fatigue or dyspnea after ordinary physical activity

Immunological

• No autoimmune disease, including the following:
  • Addison's disease
  • Hashimoto's thyroiditis
  • Systemic lupus erythematous
  • Sjögren syndrome
  • Scleroderma
  • Myasthenia gravis
  • Goodpasture syndrome
  • Active Grave's disease
• HIV negative
• No allergy or untoward reaction to prior vaccination with vaccinia virus or to any component of the vaccinia vaccine regimen
• No serious hypersensitivity reaction to egg products

Other

• During and for at least 3 weeks after vaccinia vaccination, patients or their close household contacts must not have contact with the following individuals:
  • Individuals with active or a history of eczema or other eczematoid skin disorders
  • Individuals with acute, chronic, or exfoliative skin disorders, including any of the following until the condition resolves:
    • Atopic dermatitis
    • Burns
    • Impetigo
    • Varicella zoster
    • Severe acne
    • Other open rashes or wounds
  • Pregnant or nursing women
  • Children ≤ 5 years of age
  • Individuals who are immunodeficient or immunosuppressed by disease or therapy (including HIV-infected individuals)
• No concurrent serious medical illness that would preclude study compliance, including, but not limited to, the following:
  • Inflammatory bowel disease
  • Crohn's disease
  • Ulcerative colitis
  • Active diverticulitis
• No history of seizures, encephalitis, or multiple sclerosis
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 months after study treatment

Expected Enrollment

A total of 16 patients will be accrued for this study.

Outcomes

Safety by CTC AE version 3.0

Objective response by RECIST every 2 months
Compare immunologic response by ELISPOT at baseline and day 91

Outline

Patients receive a priming vaccination of vaccinia (rV)-CEA-TRICOM and recombinant fowlpox GM-CSF (rF-GM-CSF) vaccine subcutaneously (SC) on day 1. Patients receive a booster vaccination of fowlpox (rF)-CEA-TRICOM and rF-GM-CSF SC on days 21, 35, 49, and 63. Patients undergo radiotherapy on days 22-25, 36-39, 50-53, and 64-67. Patients with stable disease or objective response after day 91 continue to receive rF-CEA-TRICOM and rF-GM-CSF SC every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed annually for 15 years.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

James Gulley, MD, PhD, Principal investigator		Ph: 301-435-2956 Email: gulleyj@mail.nih.gov

Related Information

Web site for additional information

Registry Information
Official Title		A Pilot Trial Of A CEA-Tricom Based Vaccine And Radiation To Liver Metastasis In Adults With CEA Positive Solid Tumors
Trial Start Date		2004-04-22
Registered in ClinicalTrials.gov		NCT00085241
Date Submitted to PDQ		2004-04-21
Information Last Verified		2007-01-07