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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To assess physician-reported acute grade 3 or greater gastrointestinal, genitourinary and
      hematologic toxicities at 12 weeks post-treatment for patients treated with linear energy
      transfer (LET)-optimized, intensity-modulated proton therapy (IMPT) and compare to
      contemporary controls treated with volume modulated arc therapy (VMAT) to determine the
      feasibility of this outcome for a future randomized trial.

      SECONDARY OBJECTIVES:

      I. To assess the feasibility of enrolling patients on a prospective trial delivering
      LET-optimized IMPT for newly diagnosed, non-metastatic anal cancer.

      II. To develop guidelines and workflow to create and deliver anal canal cancer treatments
      using LET-optimized IMPT.

      III. To evaluate complete response rate at 12 weeks and 24 weeks post-treatment.

      IV. To evaluate local progression free survival, distant metastasis-free survival and overall
      survival at 24 and 48 months.

      V. To evaluate rates of patient-reported acute toxicity, function, distress and quality of
      life (QOL) at 12 weeks.

      VI. To evaluate rates of patient-reported late toxicity, function, distress and QOL every 6
      months for 24 months.

      VII. To evaluate the value of proton therapy by comparing Time-Driven Activity-Based Costing
      data from the date of consultation until the date of the 12-week follow up visit
      post-treatment with contemporary controls treated with VMAT.

      EXPLORATORY OBJECTIVES:

      I. To compare dose to the pelvic bone marrow, bowel, bladder and genitalia between
      LET-optimized IMPT, traditionally-optimized IMPT and VMAT.

      II. To assess rates of leukopenia, neutropenia and lymphopenia at 12-weeks post-treatment for
      patients treated with LET-optimized IMPT and compare to contemporary controls treated with
      VMAT.

      III. To correlate white blood cell counts (WBC), absolute neutrophil counts (ANC) and
      absolute lymphocyte counts (ALC) with dose to the pelvic bone marrow for patients treated
      with LET-optimized IMPT.

      OUTLINE:

      Patients undergo linear energy transfer-optimized intensity modulated proton therapy 5 times
      per week for 5-6 weeks. Patients also receive standard cisplatin and fluorouracil
      intravenously (IV) weekly for up to 6 weeks in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 12 weeks.
    

Intervention name(s): Cisplatin; Fluorouracil; Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy; Quality-of-Life Assessment; Questionnaire Administration
Intervention type(s): Drug; Drug; Radiation; Procedure; Other
Intervention description(s): Given IV; Given IV; Undergo LET-IMPT; Ancillary studies; Ancillary studies
Other intervention name(s): Abiplatin; Blastolem; Briplatin; CDDP; Cis-diammine-dichloroplatinum; Cis-diamminedichloridoplatinum; Cis-diamminedichloro Platinum (II); Cis-diamminedichloroplatinum; Cis-dichloroammine Platinum (II); Cis-platinous Diamine Dichloride; Cis-platinum; Cis-platinum II; Cis-platinum II Diamine Dichloride; Cismaplat; Cisplatina; Cisplatinum; Cisplatyl; Citoplatino; Citosin; Cysplatyna; DDP; Lederplatin; Metaplatin; Neoplatin; Peyrone's Chloride; Peyrone's Salt; Placis; Plastistil; Platamine; Platiblastin; Platiblastin-S; Platinex; Platinol; Platinol- AQ; Platinol-AQ; Platinol-AQ VHA Plus; Platinoxan; Platinum; Platinum Diamminodichloride; Platiran; Platistin; Platosin; 5 Fluorouracil; 5 Fluorouracilum; 5 FU; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fluracil; 5-Fu; 5FU; AccuSite; Carac; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluracil; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; LET-Optimized IMPT; LET-Optimized Intensity Modulated Proton Therapy; Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT); Quality of Life Assessment
Intervention MeSH terms: Cisplatin; Fluorouracil
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment