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

Condition(s) targeted: Breast Cancer; Colorectal Cancer; Lung Cancer; Metastatic Cancer; Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

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

Phase: N/A

Status: Active, not recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
James Gulley, MD, PhD, Principal Investigator, Affiliation: National Cancer Institute (NCI)

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.

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

Study design: Treatment

Primary outcome: Safety by CTC AE version 3.0

Secondary outcome:

Objective response by RECIST every 2 months

Compare immunologic response by ELISPOT at baseline and day 91

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

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

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office, Bethesda, Maryland 20892-1182, United States

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

Web site for additional information

Starting date: April 2004
Last updated: May 23, 2008