This phase I trial studies the side effects of image-guided hyper-fractioned proton therapy
in treating patients with head and neck cancer that has spread to nearby tissue or lymph
nodes (locally advanced) and cannot be removed by surgery (unresectable). Radiation therapy
uses high energy protons to kill tumor cells and shrink tumors. The change in dose radiation
frequency and dose investigated in this study may help to better control the tumor and
prevent it from coming back or growing. The goal of this study is to test a new radiation
schedule that administers more radiation to the tumor tissue using image guided proton
therapy for patients that have a high risk of having a tumor recurrence (the tumor comes back
after treatment).
PRIMARY OBJECTIVE:
I. To assess the safety & feasibility of image guided mid-treatment hyper-fractioned
dose-escalation with proton therapy and identify the maximum tolerable dose (MTD) for the
treatment of locally advanced human papillomavirus (HPV) negative head and neck cancer.
OUTLINE:
Patients undergo radiation therapy once daily (QD) 5 days a week (Monday through Friday) for
the first 18 days and then twice daily (BID) for 15 days in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 8 weeks, 3, 6, 9, and 12
months in the first year after radiation therapy, every 4 months in the second year after
radiation therapy, and then every 9 months thereafter.
Inclusion Criteria:
- Biopsy proven diagnosis of squamous cell carcinoma of head and neck cancer originating
in the oropharynx, hypopharynx, larynx, oral cavity (base of tongue) or nasopharynx.
Clinical evidence should be documented, and may consist of imaging, endoscopic
evaluation, palpation, and should be sufficient to estimate the image tumor
characteristic of the primary tumor
- Negative for HPV by p16 immunohistochemistry (IHC) or in situ hybridization (ISH)
- Inoperable locally advances disease, i.e. stage >= III and T stage >= 2
- The primary radiotherapy, either in combination with chemotherapy or not, with
curative intent
- No head and neck surgery of the primary tumor or lymph nodes except for incisional or
excisional biopsies
- Eastern Cooperative Oncology Group (ECOG) = 0, 1, or 2
- For females of child-bearing age, a negative pregnancy test
Exclusion Criteria:
- Patients who have undergone definitive resection of their primary or nodal disease as
well as any chemotherapy or radiation therapy for their head and neck squamous cell
carcinoma (HNSCC)
- Patient that refuse or are unable to stop smoking and/or consuming alcohol during and
after radiotherapy. In addition, patients that refuse or fail tobacco and alcohol
blood test
- Patients that have no detectable no tumor in both the primary site and lymph nodes at
week 4 in treatment, because there will not be a volume to boost
- Patients unable or unwilling to give written, informed consent or to undergo magnetic
resonance imaging (MRI) imaging
- Women of childbearing potential (a woman of child-bearing potential is a sexually
mature woman who has not undergone a hysterectomy or who has not been naturally
postmenopausal for at least 24 consecutive months [i.e., who has had menses at any
time in the preceding 24 consecutive months]). Male partners must practice effective
contraception (oral, injectable, or implantable hormonal contraceptive; tubal
ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized
partner) throughout the study
- Patients unable to tolerate intravenous contrast for both computed tomography (CT) and
MRI, having an estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m^2 or any
contraindications to gadolinium-based contrast agents
- Contraindications to iron supplementation include hemochromatosis, colitis, history of
gastrointestinal (GI) bleeds, alcoholism, or liver disease. Ferumoxytol is
contraindicated in patients with evidence of iron overload and/or known
hypersensitivity to Feraheme or any of its components. Consequently, we will plan to
exclude patients who have symptoms or signs that might be caused by iron overload.
These include patients with (unexplained): arthritis (including premature
osteoarthritis), congestive heart failure or cardiomyopathy, adult-onset diabetes,
secondary hypogonadism, increased skin pigmentation, or patients with persistently
elevated serum ferritin not explained by an underlying inflammatory/systemic disease,
unless these patients demonstrate a fasting transferrin saturation =< 0.45
- Patients with any evidence of iron overload on pre-imaging laboratory studies
