The MetroHealth System

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

- Histologic Documentation: rectal adenocarcinoma, mismatch repair proficient (pMMR)

- Stage: Clinical stage II or III rectal adenocarcinoma defined as T4N0 or any T with
node positive disease (any T, N+); also T3N0 requiring abdominal perineal resection
(APR) or coloanal anastomosis

- Tumor site: Rectum; distal edge of the tumor =< 12cm from the anal verge (as
determined by surgeon's endoscopic assessment; MRI can be used to compliment this
information, but endoscopy should be the primary means of assessment)

- No prior systemic chemotherapy, targeted therapy, or immunotherapy; or radiation
therapy administered as treatment for colorectal cancer within the past 5 years is
allowed. No local approaches to excising the rectal cancer (even if done for
diagnostic purposes) are allowed (e.g., transanal excision [open or minimally
invasive], local excision, endoscopic submucosal dissection or endoscopic submucosal
resection).

- Not pregnant and not nursing, because this study involves an agent that has known
genotoxic, mutagenic and teratogenic effects

* Therefore, for women of childbearing potential only, a negative pregnancy test
(urine or serum according to institutional guidelines) done =< 14 days prior to
registration is required. Female subjects agree to use highly effective
contraception combined with an additional barrier method (e.g, diaphragm, with a
spermicide) while on study and for >= 9 months after last dose of study drug, and
the same criteria are applicable to male subjects if they have a partner of
childbirth potential. Male subject agrees to use a condom and not donate sperm while
in this study and for >= 6 months after the last treatment

- Age >= 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (or Karnofsky >=
60%)

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm

- Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine
clearance >= 50 mL/min

^3

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3 x upper limit
of normal (ULN)

- No upper rectal tumors (i.e., distal portion of tumor must be => 12 cm from the anal
verge)

- No recurrent rectal cancer; prior transanal excision, prior distal sigmoid cancer
with a low anastomosis or prior endoscopic submucosal dissection

- No known mismatch repair deficient rectal adenocarcinoma

- HIV-infected patients on effective anti-retro viral therapy with undetectable viral
load within 6 months are eligible for this trial

- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardio toxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association Functional Classification1. To
be eligible for this trial, patients should be class 2B or better

- Testing for dihydropyrimidine dehydrogenase (DPD) deficiency is not required.
However, when available, patients with complete lack of DPD should not be treated
with fluoropyrimidines (such patients must not be enrolled or if initiated on
therapy and noted to have fluoropyrimidine related toxicities be taken off protocol;
dose reductions for patients with partial deficiency may be done per local
guidelines

- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on
this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14
days prior to registration on the study

- Chronic concomitant treatment with strong CYP3A4 inducers is not allowed.
Patients must discontinue the drug 14 days prior to the start of study
treatment

- Once systemic chemotherapy has been completed and the patient is either in
surveillance or being considered for surgery then medically necessary CYP3A4
medications can be resume