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

This research study is a Phase I clinical trial, which tests the safety of an investigational
intervention and also tries to define the appropriate dose of the investigational
intervention to use for further studies. "Investigational" means that the intervention is
being studied.

Stereotactic body radiation was developed as imaging and treatment capabilities on radiation
treatment machines became more accurate and more precise. Like standard radiation therapy,
stereotactic body radiation kills tumor cells by causing small breaks in the DNA of these
cells. In this research study, the investigators are looking for the highest dose of the
stereotactic radiation that can be given safely either alone, or as a 'boost dose' in
combination with standard radiation and chemotherapy. Because stereotactic radiation is so
precise, the investigators are testing whether it can be used to increase the dose to the
primary tumor without significantly increasing the side effects; the goal is to improve the
likelihood of killing the tumor and, in some cases, to complete the course of radiation in a
shorter amount of time.

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