TAS-102 With Concurrent Radiation for the Treatment of Untreated Resectable Stage II-III Rectal Cancer

PRIMARY OBJECTIVE:

I. To determine the recommended phase 2 dose of trifluridine and tipiracil hydrochloride (TAS-102) per the proportion of grade 3 or higher adverse events during chemo-radiation therapy (CRT) with concurrent TAS-102 at the maximum tolerated dose by allowing no more than 30% grade 3 or higher adverse events.

SECONDARY OBJECTIVES:

I. Evaluate safety of participants treated with TAS-102 during radiation therapy (RT).

II. Evaluate treatment emergent adverse events (TEAEs) attributable to TAS-102 with RT during fluorouracil/leucovorin calcium/oxaliplatin (FOLFOX) or capecitabine/oxaliplatin (CAPOX) treatment.

EXPLORATORY OBJECTIVES:

I. To preliminary assess the rates of complete clinical response (cCR) by magnetic resonance imaging (MRI) and by endoscopy after TAS-102 with concurrent CRT.

II. To preliminary assess the rates of cCR by MRI and by endoscopy after treatment with FOLFOX.

III. To preliminary assess the rates of pCR after standard total mesorectal excision (TME).

OUTLINE: This is dose-escalation study of TAS-102.

Patients receive TAS-102 orally (PO) twice daily (BID) Monday-Friday on weeks 1, 3, and 5. Patients also undergo intensity modulated radiotherapy (IMRT) or 3-dimensional conformal radiotherapy (3D-CRT) 5 days per week on weeks 1-5. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care FOLFOX or CAPOX.

After completion of study treatment, patients are followed for up to a total of 16 weeks (3 months) from end of FOLFOX or CAPOX treatment until rectal cancer surgery or death, whichever occurs first. Participants that opt for a non-surgical option at the end of chemotherapy may be followed for a longer period of time.