Trial Information

A Phase II Trial of Induction Chemotherapy Followed by Cetuximab (Erbitux) With Low Dose vs. Standard Dose IMRT in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx

OBJECTIVES:

Primary

- To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and
cetuximab followed by cetuximab in combination with low-dose or standard-dose
intensity-modulated radiotherapy, as measured by 2-year progression-free survival
(PFS), in patients with HPV-associated resectable stage III-IVB squamous cell carcinoma
of the oropharynx.

Secondary

- To assess overall survival.

- To evaluate the objective response, local control, and metastatic rate.

- To evaluate early and late toxicities of treatment.

Tertiary

- To evaluate quality of life and speech and swallowing function as measured by FACT-G,
FACT-HN, and VHNSS.

- To assess the effect of treatment-induced fatigue on general physical functioning in
patients with head and neck cancer.

- To correlate functional decline with clinical, physical, and biologic correlatives.

- To evaluate radiation-resistance markers, including ERCC1 single nucleotide
polymorphism and protein expression, and to correlate them with treatment efficacy.

- To demonstrate the usefulness of biomarkers, including ERCC1, EGFR, cytokine and
chemokine markers, and plasma TGFA and TGFB levels, in predicting PFS and other outcome
parameters.

- To evaluate the correlation between the efficacy of cetuximab and polymorphisms in
FcγR-receptors.

- To evaluate functional outcome and biological parameters, including telomere length,
angiotensin-converting enzyme polymorphism, and C-reactive protein level.

OUTLINE: This is a multicenter study.

- Induction therapy: Patients receive cisplatin IV over 1 hour on day 1 and paclitaxel IV
over 3 hours and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats
every 21 days for 3 courses. Patients then undergo evaluation of response to induction
therapy. Patients with a clinical complete response (CR) at the primary tumor site
proceed to group 1 of concurrent radiotherapy and cetuximab. Patients with a clinical
partial response (PR) or stable disease (SD) at the primary tumor site or those with
grossly positive disease at the primary tumor site proceed to group 2 of concurrent
radiotherapy and cetuximab.

- Concurrent radiotherapy and cetuximab: Treatment begins 14-21 days after the last day
of induction therapy.

- Group 1 (CR): Patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5
days per week for approximately 5 weeks (27 fractions). Patients also receive
cetuximab IV over 1-2 hours once weekly for 6 weeks.

- Group 2 (PR, SD, or grossly positive disease): Patients undergo standard-dose IMRT
5 days per week for approximately 6 weeks (33 fractions). Patients also receive
cetuximab IV over 1-2 hours once weekly for 7 weeks.

Patients complete questionnaires assessing fatigue, physical function, weight loss, quality
of life, head and neck symptom burden, and speech and swallowing function at baseline and at
1, 6, 12, and 24 months after completion of study treatment.

Tumor tissue and serum samples may be collected periodically for correlative laboratory
studies.

After completion of study treatment, patients are followed up periodically for 3 years.