Cisplatin, Nab-Paclitaxel, and Cetuximab (CACTUX) in Patients With Incurable Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

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

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

- At least 18 years of age.

- ECOG performance status ≤ 1

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

- Leukocytes ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Total bilirubin ≤ 1.5 mg/dL

- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN, alkaline phosphatase ≤ 2.5 x IULN, unless bone
metastasis is present in the absence of liver metastasis

- Creatinine at or below IULN (males 0.7-1.30 mg/dl; females 0.6-1.10 mg/dl) OR
Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels
above institutional normal

- At least 4 months since completion of curative therapy, if given previously.

- Availability of diagnostic tumor tissue specimens for correlative studies.

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry, for
the duration of study participation, and for 3 months after completing treatment.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she must inform her treating physician immediately.

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

Exclusion Criteria:

- Prior systemic therapy for incurable disease.

- Grade 2 or higher peripheral neuropathy at screening.

- A history of other malignancy ≤ 2 years previous; exceptions are malignancies with a
negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) that were
treated with an expected curative outcome, such as squamous cell carcinoma of the
skin, in-situ carcinoma of the cervix uteri, non-melanomatous skin cancer, carcinoma
in situ of the breast, incidental finding of prostate cancer (TNM stage of T1a or
T1b), or synchronous H&N primaries

- Currently receiving any other investigational agents.

- Known brain metastases. Patients with known brain metastases must be excluded from
this clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to cisplatin, nab-paclitaxel, or other agents used in the study.
Previous grade 1 or 2 allergic reaction to cetuximab is permissible.

- 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 and/or breastfeeding. Patient must have a negative pregnancy test within 72
hours of start of study treatment.

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