Mitomycin C in Patients With Incurable p16 Positive Oropharyngeal and p16 Negative Head and Neck Squamous Cell Carcinoma (HNSCC) Resistant to Standard Therapies

Inclusion Criteria:

• Histologically or cytologically confirmed incurable HNSCC of the oral cavity,oropharynx, larynx, hypopharynx, and/or Level 1-3 neck node with non-cutaneous SCCand unknown primary. "Incurable" is defined as metastatic disease or a local orregional recurrence in a previously irradiated site that is unresectable (or patientdeclines resection).

• Progression following platin and immunotherapy given for incurable disease.

• Measurable disease defined as lesions that can be accurately measured in at leastone dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mmby chest x-ray, or ≥ 10 mm with calipers by clinical exam per RECIST 1.1.

• Tissue available (either initial diagnostic or recurrent tissue specimen) for p16testing.

• At least 18 years of age.

• ECOG performance status ≤ 3

• Adequate hematologic, renal, and hepatic function as defined below:

• Absolute neutrophil count ≥ 1,000/mcl

• Platelets ≥ 75,000/mcl

• Total bilirubin ≤ 1.5 mg/dL

• AST(SGOT)/ALT(SGPT) ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN, unless bonemetastasis is present in the absence of liver metastasis

• Creatinine below ULN (males 0.7-1.30 mg/dl; females 0.6-1.10 mg/dl) ORCreatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levelsabove institutional normal

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, forthe duration of study participation, and for 1 month after completing treatment.Should a woman become pregnant or suspect she is pregnant while participating inthis study, she must inform her treating physician immediately.

• Ability to understand and willingness to sign an IRB approved written informedconsent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Other active malignancy with the exception of basal cell or squamous cell carcinomaof the skin which were treated with local resection only, carcinoma in situ of thecervix, or synchronous H&N primaries.

• Currently receiving any other investigational agents.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.

• Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 7days of start of study treatment.

• Known active central nervous system (CNS) metastases. Subjects with previouslytreated brain metastases may participate provided they are stable (without evidenceof progression by imaging for at least four weeks prior to the first dose of trialtreatment and any neurologic symptoms have returned to baseline), have no evidenceof new or enlarging brain metastases, and are not using steroids for at least 28days prior to treatment.

• A history of allergic reactions attributed to compounds of similar chemical orbiologic composition to mitomycin C or other agents used in the study.

• Known HIV-positivity on combination antiretroviral therapy because of the potentialfor pharmacokinetic interactions with the study drugs. In addition, these patientsare at increased risk of lethal infections when treated with marrow-suppressivetherapy. Appropriate studies will be undertaken in patients receiving combinationantiretroviral therapy when indicated.