Houston, Texas 77030


Purpose:

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.


Study summary:

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. IV. To encourage optional co-enrollment on study 2014-0543 so that tumor deoxyribonucleic acid (DNA), rectal microbiome and magnetic resonance imaging (MRI) imaging-based biomarkers can be assessed for patients receiving LET-optimized IMPT and compared with other patients enrolled on 2014-0543 receiving VMAT-based radiation. 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.


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 14 days prior to registration - Anal examination with biopsy on either colonoscopy, sigmoidoscopy, rigid proctoscopy or anoscopy within 30 days of registration - Computed tomography (CT) scan of the chest and abdomen with contrast or contrast-enhanced positron emission tomography (PET)/CT scan within 30 days of registration unless the patient has a documented contrast allergy - CT scan of pelvis with contrast or contrast-enhanced PET/CT scan within 30 days of registration unless the patient has a documented contrast allergy - Zubrod performance status of 0-1 - Absolute neutrophil count (ANC) >=1800 cells/mm^3, cannot be achieved through granulocyte-colony stimulating factor (GCSF) (within 14 days prior to study registration) - Platelets >= 100,000 cells/mm^3, cannot be achieved through transfusion (within 14 days prior to study registration) - Hemoglobin >= 8 g/dL, cannot be achieved through transfusion (within 14 days prior to study registration) - Serum creatinine =< 1.5mg/dL (within 14 days prior to study registration) - Bilirubin =< 1.4mg/dL, except in the case of patients with Gilbert's disease (within 14 days prior to study registration) - White blood cells (WBC) >= 3000/microliter (within 14 days prior to study registration) - Aspartate transaminase (AST)/alanine transaminase (ALT) < 3 x the upper limit of normal (within 14 days prior to study registration) - International normalized ratio (INR) =< 1.5 (within 14 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


NCT ID:

NCT03690921


Primary Contact:

Principal Investigator
Emma Holliday
M.D. Anderson Cancer Center

Emma B. Holliday
Phone: 713-563-2300
Email: EBHolliday@mdanderson.org


Backup Contact:

N/A


Location Contact:

Houston, Texas 77030
United States

Emma B. Holliday
Phone: 713-563-2300

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: February 04, 2019

Modifications to this listing: Only selected fields are shown, please use the link below to view all information about this clinical trial.


Click to view Full Listing

If you would like to be contacted by the clinical trial representative please fill out the form below.