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
Primary Purpose
Anal Canal Squamous Cell Carcinoma, Stage I Anal Cancer AJCC v8, Stage II Anal Cancer AJCC v8
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Fluorouracil
Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy
Quality-of-Life Assessment
Questionnaire Administration
Sponsored by
About this trial
This is an interventional treatment trial for Anal Canal Squamous Cell Carcinoma
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
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (LET-IMPT, chemotherapy)
Arm Description
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 IV weekly for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Acute Toxicity
Number (percentage) of patients with physician-reported acute G3+ GI, GU and heme toxicities
Secondary Outcome Measures
Complete Response at 12 Weeks
Number (percentage) patients who achieved a complete clinical response of their disease by 12 weeks after chemoradiation.
Local Progression Free Survival at 24 Months
Patients alive without evidence of local progression 24 months after chemoradiation.
Distant Metastasis-free Survival at 24 Months.
Patients alive without evidence of distant metastases 24 months after chemoradiation.
Overall Survival at 24 Months
Patients alive 24 months after chemoradiation.
Complete Response at 24 Weeks
Number (percentage) patients who achieved a complete clinical response of their disease by 24 weeks after chemoradiation.
Full Information
NCT ID
NCT03690921
First Posted
September 27, 2018
Last Updated
June 9, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03690921
Brief Title
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
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
November 8, 2018 (Actual)
Primary Completion Date
June 3, 2022 (Actual)
Study Completion Date
June 3, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (LET-IMPT, chemotherapy)
Arm Type
Experimental
Arm Description
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 IV weekly for up to 6 weeks in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fluorouracil
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy
Other Intervention Name(s)
LET-Optimized IMPT, LET-Optimized Intensity Modulated Proton Therapy, Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT)
Intervention Description
Undergo LET-IMPT
Intervention Type
Procedure
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Acute Toxicity
Description
Number (percentage) of patients with physician-reported acute G3+ GI, GU and heme toxicities
Time Frame
Acute physician reported toxicity from start of treatment 12 weeks post-treatment
Secondary Outcome Measure Information:
Title
Complete Response at 12 Weeks
Description
Number (percentage) patients who achieved a complete clinical response of their disease by 12 weeks after chemoradiation.
Time Frame
12 weeks
Title
Local Progression Free Survival at 24 Months
Description
Patients alive without evidence of local progression 24 months after chemoradiation.
Time Frame
24 months
Title
Distant Metastasis-free Survival at 24 Months.
Description
Patients alive without evidence of distant metastases 24 months after chemoradiation.
Time Frame
24 months
Title
Overall Survival at 24 Months
Description
Patients alive 24 months after chemoradiation.
Time Frame
24 months
Title
Complete Response at 24 Weeks
Description
Number (percentage) patients who achieved a complete clinical response of their disease by 24 weeks after chemoradiation.
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emma B Holliday
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center
Learn more about this trial
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
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