Chemotherapy and Intensity-Modulated Radiation Therapy in Treating Patients with HPV-Associated Oropharyngeal Squamous Cell Cancer

This phase II trial studies how well chemotherapy and intensity-modulated radiation therapy work in treating patients with human papilloma virus (HPV)-associated oropharyngeal squamous cell cancer. Drugs used in chemotherapy, such as cisplatin, cetuximab, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving a lower dose of chemotherapy and radiation therapy may provide a similar cure rate as the longer, more intensive standard regimen.

Inclusion Criteria

• T0-3, N0 to N2c, M0 squamous cell carcinoma of the oropharynx (American Joint Committee on Cancer [AJCC] 7th edition)
• Biopsy proven squamous cell carcinoma that is HPV and/or p16 positive
• Radiologic confirmation of the absence of hematogenous metastasis within 12 weeks prior to treatment; at a minimum, chest x-ray is required; computed tomography (CT) imaging of the chest or positron emission tomography (PET)/CT is acceptable
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Platelets >= 100,000 cells/mm^3 (obtained within 8 weeks prior to treatment)
• Hemoglobin >= 8.0 g/dl (obtained within 8 weeks prior to treatment) (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Serum creatinine < 2.0 mg/dl (obtained within 4 weeks prior to treatment)
• Total bilirubin < 2 x the institutional upper limit of normal (ULN) (obtained within 4 weeks prior to treatment)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x the institutional ULN (obtained within 4 weeks prior to treatment) * Note that physician attestation of patient having no known history of liver disease can take the place of bilirubin and AST/ALT labs
• Negative pregnancy test within 2 weeks prior to treatment for women of childbearing potential
• Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment and for 6 weeks following treatment
• Patients must be deemed able to comply with the treatment plan and follow-up schedule
• Patients must provide study specific informed consent prior to study entry

Exclusion Criteria

• Prior history of radiation therapy to the head and neck
• Prior history of head and neck cancer
• Unresectable disease (e.g. immobile node on physical exam, nodal disease that radiographically involves the carotid arteries, nerves)
• Currently taking disease modifying rheumatoid drugs (DMRDs)
• Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months * Transmural myocardial infarction within the last 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration * Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, coagulation parameters are not required for entry into this protocol * Pre-existing >= grade 2 neuropathy * Prior organ transplant * Systemic lupus * Psoriatic arthritis
• Known human immunodeficiency virus (HIV) positive

PRIMARY OBJECTIVES:

I. To evaluate whether genomic based risk-stratification can be used in deciding whether to de-intensify in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) with > 10 pack years smoking history.

SECONDARY OBJECTIVES:

I. To prospectively assess if the changes in plasma circulating free HPV deoxyribonucleic acid (DNA) during and after treatment are associated with clinical outcomes in patients with HPV-associated OPSCC.

II. To assess the 2 year clinical outcomes of local control (LC), regional control (RC), local-regional control (LRC), distant metastasis free survival (DMFS), and overall survival (OS).

III. To compare head and neck quality of life assessments before, during, and after chemoradiotherapy (CRT).

IV. To compare speech and swallowing function before and after CRT.

OUTLINE:

Patients receive intensity-modulated radiation therapy (IMRT) daily over 6 weeks for a total of 30 fractions. Patients (except those with T0-2 N0-1 disease and =< 10 pack years smoking history) also receive chemotherapy intravenously (IV) comprising of either cisplatin, cetuximab, carboplatin and paclitaxel, or carboplatin alone during IMRT on days 1, 8, 15, 22, 29, and 36. Patients with > 10 pack years smoking history and p53 gene mutation receive 1 additional fraction of IMRT and 1 additional dose chemotherapy.

After completion of study treatment, patients are followed up at 10-16 weeks, every 2-3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.

Lead Organization
UNC Lineberger Comprehensive Cancer Center

Principal Investigator
Bhishamjit S. Chera