Official Title: “A Pilot Trial Of A CEA-Tricom Based Vaccine And Radiation To Liver Metastasis In Adults With CEA Positive Solid Tumors”

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining vaccine therapy and radiation therapy may kill more tumor cells.

PURPOSE: This clinical trial is studying how well giving vaccine therapy together with radiation therapy works in treating patients with carcinoembryonic antigen-positive solid tumors that have metastasized to the liver.

Study Type: Interventional

Study Design: Treatment

OBJECTIVES:

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

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.

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

Intervention(s) in this Clinical Trial

• Drug: recombinant fowlpox GM-CSF vaccine adjuvant
• Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine
• Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine
• Procedure: radiation therapy

Primary Measures

• Safety by CTC AE version 3.0
  • Safety Issue?: Yes

Secondary Measures

• Objective response by RECIST every 2 months
  • Safety Issue?: No
• Compare immunologic response by ELISPOT at baseline and day 91
  • Safety Issue?: No

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

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• ECOG 0-1
• Life expectancy
• At least 6 months
• Hematopoietic
• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8 g/dL
• Absolute lymphocyte count ≥ 400/mm^3
• 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

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Cancer Institute (NCI)

Overall Clinical Trial Officials and Contacts

James Gulley, MD, PhD Principal Investigator National Cancer Institute (NCI)  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00085241

Study ID Number: CDR0000367490

ClinicalTrials.gov Identifier: NCT00085241

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database

Web site for additional information