Weekly Carboplatin, Paclitaxel and Cetuximab Treatment for Patients With Recurrent or Metastatic SCCHN

Because of their high response rates and low toxicity, the taxane, carboplatin, cetuximab
regimens have frequently been adapted for use in the palliative setting. At UNC, we have
observed high rates of response, leading to symptomatic benefit and low toxicity. Further,
the regimen de-medicalizes the patient's life in several important ways. First, unlike with
the EXTREME regimen, no PORT or 4 day infusion is required. Second, the regimen gives only
six weeks of cytotoxic therapy. Finally, in our experience there is a low rate of severe
toxicity and this, coupled with the high rate of response, may improve quality of life. We
are not aware of any presented or published results on the use of this combination in
palliative therapy; with the adoption of this regimen in clinical practice, documentation of
its benefit via conduct of a clinical trial is needed.

We propose a study designed to detect an improvement in median OS versus a historical
control. The control arm from the EXTREME trial achieved a median OS of 7.4 months. We
hypothesize that a less toxic and more effective 3-drug regimen will result in improved
median OS compared with the control arm from EXTREME (median 7.4 months). The toxicity
associated with EXTREME is primarily attributable to the cisplatin and 5FU cytotoxic backbone
as its toxicity has been consistent in multiple studies of both palliative therapy and
induction therapy. If a 4-month improvement in OS is achieved with acceptable toxicity, we
will consider this regimen worth of further study.

Secondary objectives will include characterizing changes in quality of life (QoL), symptoms
and toxicities. Patients will be encouraged to co-enroll into the UNCseq protocol for further
exploration of associations between genetic changes and clinical outcomes.

Inclusion Criteria:

- Age ≥ 18 years old

- Histologically or cytologically confirmed recurrent or metastatic Squamous Cell
Carcinoma of the Head and Neck (SCCHN). All primary sites are eligible excluding WHO
type III or EBV nasopharyngeal (WHO type I and WHO type II allowed as long as they are
EBV negative)

- ECOG performance status 0-1

- Adequate organ and marrow function as defined below. Laboratory tests should be
completed within 14 days prior to registration: ANC greater than or equal to
1,500/mm3, Platelets greater than or equal to 100,000/mm3, HgB greater than 9g/dL
(acceptable to reach this by transfusion), Total bilirubin less than or equal to
1.5mg/dL, Albumin greater than 2.5 g/dL, AST(SGOT)/ALT(SGPT) less than or equal to
2.5X institutional upper limit of normal, alkaline phosphatase less than or equal to
2.5 x upper limit of normal, GFR greater than 30 mL/min (by standard Cockroft and
Gault formula or measured via 24 hour urine collection)

- Women of childbearing potential (WOCBP) with negative serum or urine pregnancy test
within 7 days of D1 of treatment

- WOCBP and men must agree to use adequate contraception prior to study entry and for
duration of treatment under this protocol; adequate contraception is defined as any
medically recommended method (or combination of methods) per standard of care.

- Cancer must be considered incurable by the treating clinician

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

Exclusion Criteria:

- History of prior cumulative exposure to > 300mg/m2 cisplatin, AUC of 18 of
carboplatin, or their combined equivalent within one year prior to enrollment

- Surgery or radiation within the four weeks prior to D1 of treatment under this
protocol

- Prior systemic chemotherapy unless it was part of definitive-intent (curative intent)
treatment more than 6 months before study entry

- Other active, invasive malignancy requiring ongoing therapy or expected to require
systemic therapy within two years; localized squamous cell carcinoma of the skin,
basal-cell carcinoma of the skin, carcinoma in-situ of the cervix, or other
malignancies requiring locally ablative therapy only will not result in exclusion

- Pregnant or lactating female