This study will determine the safety of injecting a fowlpox virus vaccine into tumors of the mouth and throat. It will also examine the effects of the vaccine on the tumor and immune system. The vaccine is manufactured through genetic engineering, in which human genetic material (DNA) is inserted into fowlpox virus. The incorporation of human DNA into the virus makes what is called a "recombinant" virus that produces proteins known to help activate immune cells against cancers. The fowlpox virus itself is not known to cause disease in humans.

Patients with advanced tumors of the mouth and throat that cannot be treated successfully with standard therapies, such as surgery or radiation therapy, may be eligible for this 3-month study. Candidates will be evaluated with a history and physical examination, tumor measurements, blood tests, electrocardiogram, urinalysis, speech and swallowing evaluation, and skin tests to assess immune function. Those enrolled will have imaging procedures, such as bone scans, X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI) or ultrasound to evaluate the tumor before starting treatment.

Patients will undergo staging endoscopy and biopsy. This is done under general anesthesia in the operating room. A tube with a light at the tip is inserted into the mouth to examine the tumor and a small sample of tumor tissue is removed for examination under the microscope. During the procedure, the fowlpox virus vaccine will be injected directly into the tumor through the mouth. Patients will remain in the hospital overnight for observation. Blood samples will be collected immediately before the procedure and during the following day.

Patients will have a history and physical examination every week for 5 weeks and again at week 8, with blood tests and tissue samples taken at some of the visits. A "booster" vaccine will be injected directly into the tumor through the mouth 3 weeks after the first injection. This will be done either in the clinic with the patient awake or in the operating room with the patient sedated. The staging endoscopy and biopsy will be repeated after 5 weeks to analyze the effect of the vaccine on the tumor.

Patients whose cancer worsens or who develop serious harmful side effects will be taken off the study. Those who remain will be offered booster injections every 8 weeks. History and physical examinations and blood tests will be done every 2 weeks and eligibility to continue will be re-evaluated every 8 weeks. Those who respond well to therapy may continue beyond 3 months.

Condition	Treatment or Intervention	Phase
Squamous Cell Carcinoma	Drug: Recombinant Fowlpox TRICOM	Phase I

Further Study Details: 

Expected Total Enrollment:  20

This is a phase I study designed to evaluate the toxicity of a recombinant pox virus engineered to express a triad of costimulatory molecules in patients with advanced head and neck squamous cell carcinoma. The study will evaluate the hypothesis that intralesional administration of a recombinant fowlpox vector, containing a TRIad of COstimulatory Molecules (designated rF-TRICOM) into the primary tumor of patients with squamous cell carcinoma involving the oral cavity, oropharynx, or nodal or dermal metastases is feasible. Patients with recurrent disease who have exhausted standard treatment options and/or those patients with unresectable metastatic disease will be eligible. Tolerance of this regimen will be judged by using RTOG and CTEP standard toxicity criteria. Tissue biopsies and samples will be obtained before and after administration of rF-TRICOM to measure gene expression as well as biological effects.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA
Age greater than or equal to 18 years.
Patients with stage IV histologically-proven squamous cell carcinoma of the oral cavity, oropharynx or nodal or dermal metastases, may be eligible provided that currently available treatment is not likely to offer a survival advantage or result in significant palliation. Specifically, patients with unresectable locoregional recurrence following maximal radiation treatment, and those with local disease and unequivocal evidence of unresectable distant metastases, are eligible. Criteria for unresectability includes involvement of: a) the base of skull, b) prevertebral fascia, c) deep neck muscles, d) the carotid artery (that would require resection), e) the nasopharynx and/or pterygoid muscles.
Primary intraoral lesions must be measurable and accessible to intralesional injections.
Patients must have a Zubrod (ECOG) performance status of 0-2.
Women of childbearing potential must have a negative serum Beta-HCG and should be instructed in and agree to use adequate contraception while participating in the study.
Patients with prior history of surgery for management of the primary or metastatic lesions will be eligible to enter the study if more than 4 weeks have elapsed from the time of surgery and the patient has fully recovered and as long as there still remains measurable disease. Patients with metastatic brain lesions, leptomeningeal disease or seizure disorder are ineligible.
Patients with a prior history chemotherapy may be eligible for inclusion, if the following criteria are met:
a) no more than 2 prior chemotherapy regimens;
b) greater than or equal to 4 weeks have elapsed since the last cycle;
c) they have fully recovered from any associated toxicity.
Patients with a prior history of radiation treatment may be eligible for inclusion, if the following criteria are met:
a) they are ineligible to receive radiation treatment to the head and neck during the study;
b) greater than or equal to 4 weeks have elapsed since receiving radiation;
3) the patient has fully recovered from any acute toxicity.
Patients with a prior history of immunotherapy may be eligible for inclusion, provided that:
a) greater than or equal to 4 weeks have elapsed since prior therapy;
b) no evidence of toxicity related to prior therapy.
Patients must have a life expectancy greater than or equal to 2 months at the start of trial.
Patients must have adequate physiology as measured by:
a) ANC greater than 1,000/mm(3);
b) PT, PTT must be less than 1.5 X UNL;
c) Plt greater than 100,000/mm(3);
d) Hgb greater than 8 gm/dL;
e) Serum Creatinine less than 2.0 mg/dL or creatinine clearance greater than 60cc/min;
f) Direct bilirubin less than 1.5 mg/dL;
g) AST, ALT less than 4X upper limit of normal (ULN);
h) No evidence of congestive heart failure, serious cardiac dysrhythmia, no evidence of recent prior myocardial infarction on EKG, no clinical coronary artery disease.
Patients must sign an informed consent form indicating that they understand the nature of their disease, treatment options, the experimental nature of this study, the risks, possible side effects, any discomforts, and potiential benefit of entering the study as outlined in this protocol.
EXCLUSION CRITERIA
Patients who are at risk for immune compromise are excluded, including those with:
Reactive HIV testing.
Prior radiation therapy to greater than 50% of nodal groups.
Prior splenectomy.
Systemic corticosteroid use concurrently, within 4 weeks prior to registration or a high likelihood for its required use during the study period for the treatment of intercurrent illness.
Patients with hypersensitivity to eggs or a significant history of allergy (i.e. anaphylaxis or angioedema) are excluded.
Patients with active or chronic infections, which would interfere with the ability to receive vaccination with live virus, are ineligible. These patients may become eligible once the infection has been contained.
Patients with serious intercurrent medical illnesses, which would interfere with the ability to receive vaccination with live virus, are excluded.
Pregnant or nursing women are excluded.
Patients with a history of seizures or evidence of encephalitis, cerebral metastasis, multiple sclerosis or other structural brain lesions, by clinical or radiological evaluations, are not eligible.
Patients with a history of another type of malignancy ineligible, unless the previous tumor was treated with curative intent and there is no evidence of persistent or recurrent disease.

Maryland
      National Institute on Deafness and Other Communication Disorders (NIDCD), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States

Study ID Numbers:  010006; 01-DC-0006
Record last reviewed:  April 1, 2003
Last Updated:  April 1, 2003
Record first received:  October 13, 2000
ClinicalTrials.gov Identifier:  NCT00006410
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08