Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT) as a Component of Definitive Chemoradiation for Newly Diagnosed Squamous Cell Carcinoma of the Anal Canal: a Feasibility Trial
Condition: Anal Canal Squamous Cell Carcinoma; Stage I Anal Cancer AJCC v8; Stage II Anal Cancer AJCC v8; Stage IIA Anal Cancer AJCC v8; Stage IIB Anal Cancer AJCC v8; Stage III Anal Cancer AJCC v8; Stage IIIA Anal Cancer AJCC v8; Stage IIIB Anal Cancer AJCC v8; Stage IIIC Anal Cancer AJCC v8
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Anus Neoplasms
Intervention: Cisplatin; Fluorouracil; Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy; Quality-of-Life Assessment; Questionnaire Administration
Intervention description: Given IV; Given IV; Undergo LET-IMPT; Ancillary studies; Ancillary studies
Intervention MeSH terms: Cisplatin; Fluorouracil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects of LET-IMPT and standard chemotherapy, and how
      well they work in treating patients with newly diagnosed stage I-III anal canal squamous cell
      cancer. LET-IMPT is a type of radiation therapy that uses high energy proton "beamlets" to
      "paint" the radiation dose into the target and may help to kill tumor cells and shrink
      tumors. Giving LET-IMPT and standard chemotherapy may work better in treating patients with
      anal canal squamous cell cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically-proven, non-metastatic invasive primary squamous cell carcinoma of the
             anal canal (stages I, II, and III)

          -  History/physical examination including documentation of the primary anal lesion size,
             distance from the anal verge and anal sphincter tone within 60 days prior to
             registration

          -  Anal examination with biopsy on either colonoscopy, sigmoidoscopy, rigid proctoscopy
             or anoscopy

          -  Computed tomography (CT) scan of the chest and abdomen with contrast or
             contrast-enhanced positron emission tomography (PET)/CT scan within 60 days of
             registration unless the patient has a documented contrast allergy

          -  CT scan of pelvis with contrast or contrast-enhanced PET/CT scan within 60 days of
             registration unless the patient has a documented contrast allergy

          -  Zubrod performance status of 0-1 within 60 days prior to registration

          -  Absolute neutrophil count (ANC) >=1.8 K/ul, cannot be achieved through
             granulocyte-colony stimulating factor (GCSF) (within 30 days prior to study
             registration)

          -  Platelets >= 100 K/uL, cannot be achieved through transfusion (within 30 days prior to
             study registration)

          -  Hemoglobin >= 8 g/dL, cannot be achieved through transfusion (within 30 days prior to
             study registration)

          -  Serum creatinine =< 1.5 mg/dL (within 30 days prior to study registration)

          -  Bilirubin =< 1.4 mg/dL, except in the case of patients with Gilbert's disease (within
             30 days prior to study registration)

          -  White blood cells (WBC) >= 3000/microliter (within 30 days prior to study
             registration)

          -  Aspartate transaminase (AST)/alanine transaminase (ALT) < 3 x the upper limit of
             normal (within 30 days prior to study registration)

          -  International normalized ratio (INR) =< 1.5 (within 30 days prior to study
             registration)

          -  Human Immunodeficiency Virus (HIV) test must be done within 30 days of study
             registration. If HIV positive, CD4 count must be obtained within 30 days of study
             registration

               -  Note: HIV positive patients are eligible for this study if they have a CD4 count
                  > 400 cells/mm^3

          -  The patient must either have insurance authorization or otherwise secure funding to
             cover IMPT

          -  The patient must be able to receive concurrent chemotherapy

        Exclusion Criteria:

          -  Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free
             for a minimum of 3 years

          -  Prior systemic chemotherapy for anal cancer

          -  Prior radiotherapy to the pelvis that would result in overlap of radiation fields

          -  Evidence of distant metastatic disease (M1)

          -  Prior surgery to the anal canal that removed all macroscopic anal cancer

          -  Women of childbearing potential or men who do not agree to use a medically effective
             form of birth control throughout their participation in the treatment phase of the
             study

          -  Severe, active co-morbidity defined as follows: unstable angina and/or congestive
             heart failure requiring hospitalization within the last 6 months; transmural
             myocardial infarction within the last 6 months; acute bacterial or fungal infection
             requiring intravenous antibiotics at the time of registration; chronic obstructive
             pulmonary disease exacerbation or other respiratory illness requiring hospitalization
             or precluding study therapy at the time of registration; hepatic insufficiency
             resulting in clinical jaundice and/or coagulation defects; HIV positive with a CD4
             count < 400 cells/mm^3; other immuno-compromised status; women who are pregnant or
             lactating; uncontrolled infection as deemed by the principal investigator (PI);
             patient incarceration