TAS-102 and Radiation Therapy in Treating Patients With Rectal Cancer That Is Locally Recurrent, Metastatic, or Cannot Be Removed by Surgery

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose and dose-limiting toxicity of TAS-102 when
administered in combination with concurrent radiation therapy in patients with locally
recurrent or metastatic rectal cancer.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (ORR) to concurrent TAS-102 and radiation therapy
in patients with locally recurrent or metastatic rectal cancer.

II. To determine the progression-free survival (PFS) in patients with locally recurrent or
metastatic rectal cancer who receive concurrent TAS-102 and radiation therapy.

III. To determine the overall survival (OS) in patients with locally recurrent or metastatic
rectal cancer who receive combined TAS-102 and radiation therapy.

IV. To determine quality of life (QoL) among patients with locally recurrent or metastatic
rectal cancer who receive concurrent TAS-102 and radiation therapy.

V. To determine the number of patients who are able to undergo surgical resection following
concurrent treatment with TAS-102 and radiation therapy. Of this subset of patients, the
investigators will assess rates of pathologic complete response (pCR), tumor regression grade
(TRG) and rates of R0 resection.

OUTLINE: This is a dose-escalation study of trifluridine/tipiracil hydrochloride combination
agent TAS-102.

Patients receive trifluridine/tipiracil hydrochloride combination agent TAS-102 orally (PO)
twice daily (BID) and undergo radiation therapy in 10 fractions on days 1-5 and 8-12 in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4-6 weeks, and at 3 and 6
months.

Inclusion Criteria:

- Histological or cytological confirmation of locally recurrent or metastatic rectal
adenocarcinoma

- Note: Patients with locally recurrent/persistent disease within the pelvis after
primary therapy (chemotherapy, surgery, and/or radiotherapy) are eligible

- Note: Patients who have had prior pelvic radiotherapy with a total dose of =< 54
Gy are eligible

- Note: Patients with or without metastatic disease (excluding untreated central
nervous system [CNS] metastasis), with primary pelvic disease or pelvic
recurrence are eligible

- Note: Patients with pelvic disease that is potentially resectable or unresectable
are eligible

- Measurable disease

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Expected life expectancy >= 12 weeks

- Obtained =< 14 days prior to registration: Absolute neutrophil count (ANC) >=
1500/mm^3

- Obtained =< 14 days prior to registration: Platelet count >= 100,000/mm^3

- Obtained =< 14 days prior to registration: Hemoglobin >= 9.0 g/dL

- Obtained =< 14 days prior to registration: Total bilirubin =< 1.5 x upper limit of
normal (ULN) (in patients with well-documented Gilbert's syndrome and the total
bilirubin is grade 1, then direct bilirubin value must be =< 1.0 mg/dL)

- Obtained =< 14 days prior to registration: Aspartate transaminase (AST) =< 2 x ULN (=<
5 x ULN for patients with liver involvement)

- Obtained =< 14 days prior to registration: Alanine aminotransferase (ALT) =< 2 x ULN
(=< 5 x ULN for patients with liver involvement)

- Obtained =< 14 days prior to registration: Alkaline phosphatase =< 3 x ULN

- Obtained =< 14 days prior to registration: Creatinine =< 1.5 x ULN OR

- Obtained =< 14 days prior to registration: Calculated creatinine clearance must be >=
45 ml/min using the Cockcroft-Gault formula

- Negative pregnancy test done =< 7 days prior to registration, for women of
childbearing potential only; Note: patients must agree to adequate birth control
during the study and for up to 6 months after discontinuation of study medication

- Patients must be able to take medications orally (i.e. no feeding tube)

- Provide written informed consent

- Willing to return to enrolling institution for follow-up (during the Active Monitoring
Phase of the study)

- Able to complete questionnaires by themselves or with assistance

Exclusion Criteria:

- Primary resectable rectal cancer

- Prior treatment with TAS-102

- Chemotherapy or immunotherapy =< 28 days prior to registration

- Radiation therapy =< 28 days prior to registration; Note: patients with prior pelvic
radiation therapy > 54 Gy are ineligible

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- Other concurrent chemotherapy, immunotherapy, or any ancillary antitumor therapy
considered investigational (utilized for a non-Food and Drug Administration
[FDA]-approved indication and in the context of a research investigation)

- Untreated CNS or leptomeningeal metastasis

- Note: CNS or leptomeningeal disease must be stable for >= 3 months prior to
registration

- History of seizure disorder

- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
of the investigator, would make the patient inappropriate for entry into this study or
interfere significantly with the proper assessment of safety and toxicity of the
prescribed regimens

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Ascites, pleural effusion, or pericardial fluid requiring drainage in the last 4 weeks
prior to registration

- Intestinal obstruction, uncontrolled gastrointestinal hemorrhage, pulmonary fibrosis,
renal failure, liver failure, or cerebrovascular disorder

- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome
(AIDS)-related illness, or hepatitis B or C

- Patients with autoimmune disorders or history of organ transplantation who require
immunosuppressive therapy

- History of myocardial infarction =< 12 months prior to registration, severe/unstable
angina, systematic congestive heart failure (CHF) New York Heart Association
classification III or IV or CHF requiring use of ongoing maintenance therapy for
life-threatening ventricular arrhythmias

- Major surgery =< 4 weeks prior to registration (the surgical incision should be fully
healed prior to drug administration or radiation therapy)

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception