De-Escalation Therapy for Human Papillomavirus Negative Disease

Carboplatin will be given through IV infusions for 30-60 minutes on day 1 of each cycle. Each cycle will last 21 days. There will be 3 cycles.

"During Induction Therapy Paclitaxel (100 mg) will be given through IV infusions on days 1, 8 and 15 of each 21 day cycle. There will be 3 cycles.~During Radiotherapy, paclitaxel will be given after a dose of radiation by IV infusion for 60 minutes after day 1 of radiotherapy."

Nivolumab will be given through IV infusions at 360 mg on day 1 every 21 days for 3 cycles.

Patients will receive 4.5-5 cycles of radiation depending on response. Those with a positive response will receive radiation for 4.5 cycles with a total radiation dose of 66 Gy. Patients with a moderate or no response will receive 5 cycles with a total radiation dose of 70-75 Gy. 2 times a day for days 1-5 followed by a rest period for days 6-13

One dose of hydroxyurea pill by mouth at start of 5-FU infusion during radiotherapy cycle

5-FU will be given by IV infusion continuously for 5 days during radiotherapy cycles

Filgrastim shot will be given if patient has certain side effects during radiotherapy cycle on days 6-12.

Radiotherapy may also be given with a different chemotherapy agent called cisplatin. This is the traditional standard of care chemotherapy regimen. In this case, the radiotherapy will be given once daily for 5 days per week. Cisplatin will be administered via IV once every 21 days for 2 or 3 cycles.