Study: NCT03743662

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Re-irradiation (RT)
Description: Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period.

Intervention type: RADIATION
Group type: EXPERIMENTAL
Intervention: Re-irradiation (RT)
Description: Re-RT will start on day 28 +/- 5 days for 5 fractions of 600cGy every other day over a 2-week period.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Bevacizumab
Description: Bevacizumab if deemed beneficial by the investigator, will be started at the initiation of re-RT and continued for three doses in the medical arm. Patients in the surgical arm will omit the first bevacizumab dose to assure adequate wound healing after surgery and receive two doses. Bevacizumab will be dosed at 10mg/kg and given intravenously on day 28 (medical arm only), day 42 and day 56. Following day 56, further bevacizumab doses can be given every two weeks at the discretion of the treating physician.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Bevacizumab
Description: Bevacizumab if deemed beneficial by the investigator, will be started at the initiation of re-RT and continued for three doses in the medical arm. Patients in the surgical arm will omit the first bevacizumab dose to assure adequate wound healing after surgery and receive two doses. Bevacizumab will be dosed at 10mg/kg and given intravenously on day 28 (medical arm only), day 42 and day 56. Following day 56, further bevacizumab doses can be given every two weeks at the discretion of the treating physician.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Nivolumab
Description: Nivolumab will be started at enrollment and each patient will receive two doses of nivolumab prior to radiation.~Nivolumab will be dosed at 3mg/kg given intravenously before re-RT (day 1 +/- 5 and 14 +/- 5) and when given with bevacizumab if deemed beneficial by the investigator, (day 28 +/- 5 (medical arm only), day 42 +/- 5, and day 56 +/-5). Nivolumab will be dosed based on body weight while combined with re-radiation and bevacizumab for safety considerations to reduce adverse events. Single agent nivolumab will be given at 240mg flat dose every 2 weeks thereafter until disease progression, withdrawal, adverse event, or death.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Nivolumab
Description: Nivolumab will be started at enrollment and each patient will receive two doses of nivolumab prior to radiation.~Nivolumab will be dosed at 3mg/kg given intravenously before re-RT (day 1 +/- 5 and 14 +/- 5) and when given with bevacizumab if deemed beneficial by the investigator, (day 28 +/- 5 (medical arm only), day 42 +/- 5, and day 56 +/-5). Nivolumab will be dosed based on body weight while combined with re-radiation and bevacizumab for safety considerations to reduce adverse events. Single agent nivolumab will be given at 240mg flat dose every 2 weeks thereafter until disease progression, withdrawal, adverse event, or death.

Intervention type: PROCEDURE
Group type: EXPERIMENTAL
Intervention: Re-resection
Description: Re-resection will be performed in the surgical arm at day 14 (+/- 5 days).