A Randomized Phase II Study of De-Intensified ChemoRadiation for Early-Stage Anal Squamous Cell Carcinoma (DECREASE).

Inclusion Criteria

- Patient must have histologically proven T1-2N0M0 invasive anal canal or anal margin

squamous cell carcinoma with tumors measuring =< 4 cm within 4 weeks prior to

randomization. This may include tumors of non-keratinizing histology such as basaloid,

transitional cell or cloacogenic histology. Patients with T1N0M0 anal margin squamous

cell carcinoma who underwent surgical excision with negative margins are not eligible

- Patients who are human immunodeficiency virus (HIV)-negative must not have lymph nodes

that are radiographically-concerning for cancer involvement using computed tomography

(CT) and positron emission tomography (PET)/CT-based criteria. Measurable disease is

not required

- Patients who are HIV-negative and do not have lymph nodes classified as lymph

node positive, but are felt to be borderline for cancer involvement must undergo

central imaging review

- NOTE: Patients requiring central imaging review will be pre-registered to

Arm S. Upon central confirmation of no lymph node involvement, eligible

patients may proceed to randomization on Step 1

- Patients will be considered to be lymph node (LN) positive and thereby not

eligible in this study if the lymph nodes meet any of the following criteria:

- Mesorectal, presacral, internal iliac or obturator LN with:

- Short axis measuring > 5 mm based on CT / magnetic resonance imaging

(MRI) OR

- Morphologic features of irregular border or central necrosis if

assessed on MRI and LN measures > 3 mm OR

- Fludeoxyglucose F-18 (FDG) uptake > blood pool (Deauville 3-5) based on

PET/CT

- External Iliac and common Iliac:

- Short-axis measuring > 1 cm based on CT / MRI OR

- Morphologic features of irregular border or central necrosis based on

CT / MRI OR

- FDG uptake > blood pool (Deauville 3-5) based on PET/CT

- Inguinal LN (superficial and deep) meeting any of the following criteria will be

ineligible unless an FNA is performed and resulting cytology is negative.

- Morphologic features of irregular border or central necrosis based on CT /

MRI

- FDG uptake > liver (Deauville 4) based on PET/CT.

- Patients who are HIV-negative and have inguinal lymph nodes that do not meet

the above criteria must undergo fine needle aspiration and have negative

histology to be eligible.

- Patients who are HIV-positive must have

- A CD4 count >= 300

- Confirmation of no lymph node involvement by central real-time review of imaging

- NOTE: Patients will be pre-registered to Arm S. Upon central confirmation of

no lymph node involvement, eligible patients may proceed to randomization on

Step 1

- Patient must have Eastern Cooperative Oncology Group (ECOG) - American College of

Radiology Imaging Network (ACRIN) performance status of 0-2

- Patient must have no history of prior radiation or chemotherapy for this malignancy

- Patient must not have had prior potentially curative surgery (i.e. abdominal-perineal

resection) for carcinoma of the anus

- Patients with excisional biopsy procedure are eligible provided there was tumor

involvement of the anal canal and/or anal verge prior to resection

- Patient must not be receiving any other standard anti-cancer therapy or experimental

agent concurrently with the study drugs

- Patient must not have intercurrent illness including, but not limited to, ongoing or

active infection or psychiatric/social situations that, in the judgement of the

investigator, would limit compliance with study requirements

- Patient must not have had significant cardiovascular disease including myocardial

infarction, unstable angina, stroke, transient ischemic attack, symptomatic coronary

artery disease, symptomatic congestive heart failure, or uncontrolled cardiac

arrhythmia within 6 months of randomization

- Patient must not have a history of a different malignancy unless they have been

disease-free for at least 2 years and are deemed by the investigator to be at low risk

of recurrence

- Individuals with the following cancers are eligible if diagnosed and treated

within the past 5 years: cervical cancer in situ and basal cell or squamous cell

carcinoma of the skin

- Patient must not have active autoimmune or connective disease

- Patients who are on anti-coagulation with warfarin within 2 weeks prior to

registration and are considering the use of capecitabine, must use an alternative

anti-coagulant

- NOTE: Low molecular weight heparin is permitted provided the patient's

prothrombin time (PT)/international normalized ratio (INR) is < 1.5

- Patients who will receive capecitabine and are on Dilantin for a seizure disorder must

have Dilantin levels checked weekly

- Hemoglobin > 10 g/dL (within 2 weeks prior to registration)

- Platelets >= 100,000/mm^3 (within 2 weeks prior to registration)

- Absolute neutrophil count >= 1500/mm^3 (within 2 weeks prior to registration)

- Serum creatinine must be < 1.5 X upper limit of normal (ULN), or calculated creatinine

clearance must be > 60 ml/min (within 2 weeks prior to registration)

- Total bilirubin must be < 2 X ULN (within 2 weeks prior to registration)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X institutional

ULN (within 2 weeks prior to registration)

- Albumin >= 3.0 g/dL (within 2 weeks prior to registration)

- Women must not be pregnant or breast-feeding because the study treatment administered

may cause harm to an unborn fetus or breastfeeding child. All females of childbearing

potential must have a blood test or urine study within 2 weeks prior to registration

to rule out pregnancy. A female of childbearing potential is any woman, regardless of

sexual orientation or whether they have undergone tubal ligation, who meets the

following criteria: 1) has achieved menarche at some point, 2) has not undergone a

hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal

(amenorrhea following cancer therapy does not rule out childbearing potential) for at

least 24 consecutive months (i.e., has had menses at any time in the preceding 24

consecutive months)

- Women of childbearing potential and sexually active males must be strongly advised to

use accepted and effective method(s) of contraception or to abstain from sexual

intercourse for the duration of their participation in the study and for at least 6

months after the completion of treatment