Phase I Study Evaluating a Stereotactic Boost/Treatment for Recurrent or Metastatic Cancer of the Head and Neck

This research study seeks to gain new knowledge about the addition of a carefully
targeted "boost" dose of radiation as a possible treatment for recurrent or metastatic
head or neck cancer. The name of the study intervention involved in this study is
stereotactic body radiotherapy, which is a way of delivering radiation in a more
precisely targeted way and with a higher dose than conventional radiotherapy.

Inclusion Criteria:

- Participants must meet the following criteria on screening examination to be
eligible to participate in the study:

- All cohorts:

- Participants must have a pathologic cancer diagnosis.

- No other active malignancy within the past 2 years, except for non-melanoma skin
cancers or carcinoma in situ of the cervix.

- Only patients 18 years and older are eligible. There is no upper age limit but the
patients must be able to medically tolerate the regimen. Adverse event data are
currently unavailable on the use of SBRT for participants < 18 years of age, and
thus children are excluded from this study.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (see Appendix A).

- Ability to understand and the willingness to sign a written informed consent
document

- Cohort 1 (reirradiation in patients with head and neck cancers with gross
unresectable disease):

- History of radiation to the head and neck area (defined as above the clavicles)
greater than 6 months previous

- Pathologically proven recurrent disease or a second primary (squamous cell carcinoma
of the head and neck, nasopharyngeal cancer, salivary gland cancer, or thyroid
cancer) within the head and neck region, deemed to be unresectable or resected with
gross residual disease remaining (determined by either operative/pathology report or
post-surgical imaging)

- Participants must have normal organ and marrow function as defined below:

- Leukocytes ≥ 3,000/mcL (microliter)

- Absolute neutrophil count > ↓1,500/mcL (microliter)

- Platelets ≥100,000/mcL (microliter)

- Total bilirubin within normal institutional limits

- aspartate aminotransferase (AST (SGOT))/alanine aminotransferase (ALT (SGPT)) ≤
2.5 x institutional upper limit of normal

- Creatinine < 2 x upper limit of normal (ULN) or creatinine clearance ≥45
mL/min/1.73 m2 for subjects with creatinine levels above institutional normal

- Cohort 2 (patients with metastatic disease with targetable lesions within the head
and neck):

- Pathologically proven solid tumor (lymphomas excluded) with evidence of
metastatic disease (including nodal disease)

- Measurable disease within the head and neck region, defined as at least one
lesion that can be accurately measured in at least one dimension (longest
diameter to be recorded) as ≥10 mm and < 60 mm with neck CT scan. See section
10 for the evaluation of measurable disease.

Exclusion Criteria:

- Participants who exhibit any of the following conditions at screening will not be
eligible for admission into the study.

- SBRT target size > 6 cm in maximum diameter (or greater than 100 cc in volume).

- Participants may not be receiving any other study agents.

- Uncontrolled intercurrent illness including but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements.

- Pregnant women are excluded from this study because radiotherapy has the potential
for teratogenic or abortifacient effects. Because there is an unknown but potential
risk of adverse events in nursing infants secondary to treatment of the mother with
SBRT, breastfeeding should be discontinued if the mother is treated with SBRT.

- Individuals with a history of a different malignancy are ineligible except for the
following circumstances: if they have been disease-free for at least 2 years and are
deemed by the investigator to be at low risk for recurrence of that malignancy; or
if diagnosed and treated within the past 2 years for cervical cancer in situ or
basal cell or squamous cell carcinoma of the skin.

- HIV-positive individuals on combination antiretroviral therapy are ineligible
because of the potential for interaction between conventional radiotherapy, SBRT and
antiretroviral medications. In addition, these individuals are at increased risk of
lethal infections when treated with marrow-suppressive therapy. Appropriate studies
will be undertaken in participants receiving combination antiretroviral therapy when
indicated.

- Patients who are planned to receive the following medications:

- Granulocyte stimulating factor (G-CSF)

- Bevacizumab

- Cyclosporine

- Anti-tumor necrosis factor agents

- Amifostine