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LET-IMPT and Standard Chemotherapy in Treating Patients With Newly Diagnosed Stage I-III Anal Canal Squamous Cell Cancer

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ClinicalTrials.gov Identifier: NCT03690921
Recruitment Status : Recruiting
First Posted : October 1, 2018
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Drug: Cisplatin Drug: Fluorouracil Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy Procedure: Quality-of-Life Assessment Other: Questionnaire Administration Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 8, 2018
Estimated Primary Completion Date : May 23, 2022
Estimated Study Completion Date : May 23, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (LET-IMPT, chemotherapy)
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.
Drug: Cisplatin
Given IV
Other Names:
  • 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

Drug: Fluorouracil
Given IV
Other Names:
  • 5-Fluoro-2,4(1H, 3H)-pyrimidinedione
  • 5-Fluorouracil
  • 5-Fluracil
  • 5-FU
  • AccuSite
  • Carac
  • Fluoro Uracil
  • Fluouracil
  • Flurablastin
  • Fluracedyl
  • Fluracil
  • Fluril
  • Fluroblastin
  • Ribofluor
  • Ro 2-9757
  • Ro-2-9757

Radiation: Linear Energy Transfer-Optimized Intensity Modulated Proton Therapy
Undergo LET-IMPT
Other Name: LET-Optimized Intensity Modulated Proton Therapy; LET-Optimized IMPT; Linear Energy Transfer (LET)-Optimized Intensity Modulated Proton Therapy (IMPT)

Procedure: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Physician-reported acute grade 3 or greater gastrointestinal, genitourinary and hematologic toxicities graded according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: At 12 weeks post-treatment ]
    Will tabulate results by type, grade, and attribution and compare with contemporary controls treated with standard-care volumetric modulated arc therapy (VMAT)-based chemoradiation with cisplatin and fluorouracil. Toxicity rates will be compared using a McNemar's chi-squared test for paired proportions. Subset analyses will be carried out to evaluate the effect of other variables that may also impact toxicity in addition to radiation modality.


Secondary Outcome Measures :
  1. Feasibility as determined by number of patients enrolled [ Time Frame: Up to 24 months ]
    Will assess accrual at 24 months after study open to determine feasibility of enrolling 40 patients and obtaining insurance approval for intensity modulated proton therapy (IMPT) treatment over the planned 4 years.

  2. Guidelines and workflow development to create and deliver anal canal cancer treatments using linear energy transfer (LET)-optimized IMPT [ Time Frame: Up to 12 weeks post-treatment ]
    Will present results of workflows in a descriptive manner.

  3. Complete response defined as no evidence of disease by physical exam, endoscopy, and cross-sectional imaging [ Time Frame: At 12 and 24 weeks post-treatment ]
    Will be reported at 12 and 24 weeks post-treatment as determined clinically by physical exam, endoscopic examination and imaging.

  4. Local progression-free survival (LPFS) [ Time Frame: At 24 and 48 months ]
    LPFS is defined as either the recurrence of disease in the anal canal following clearance, progression of disease in the anal canal after completion of treatment or persistence of disease in anal canal for more than 6 months after completion of treatment. Will be estimated using the Kaplan-Meier method and estimates will be reported using 95% confidence intervals. The date of failure will be recorded as 6 months after completion of treatment in the case of persistent, biopsy-proven disease after 6 months status-post completion of all therapy.

  5. Distant metastatic failure as determined by the appearance of distant metastatic disease [ Time Frame: At 24 and 48 months ]
    Will be estimated using the Kaplan-Meier method and estimates will be reported using 95% confidence intervals. The date of failure will be recorded as 6 months after completion of treatment in the case of persistent, biopsy-proven disease after 6 months status-post completion of all therapy.

  6. Disease-free survival [ Time Frame: The time to locoregional failure, appearance of distant metastases, or death due to any cause, assessed at 24 and 48 months ]
    Will be estimated using the Kaplan-Meier method and estimates will be reported using 95% confidence intervals.

  7. Overall survival [ Time Frame: Baseline to death due to any cause, assessed at 24 and 48 months ]
    Will be estimated using the Kaplan-Meier method and estimates will be reported using 95% confidence intervals.

  8. Patient-reported acute toxicity, function, distress and quality of life (QOL) [ Time Frame: At 12 weeks post-treatment ]
    Will use Patient-Reported Outcomes (PRO) CTCAE, European Quality of Life-5 Dimensions (EQ 5D), and European Organization for Research and Treatment of Cancer Quality of Life Anal (EORTC QLQ-ANL 27), Female Sexual Function Index (FSFI), and Erectile Function Questionnaires (IIEF). The study will summarize and graph the distribution of scores for each instrument over time and analyze changes over time using mixed effects linear models.

  9. Patient-reported acute toxicity, function, distress and QOL [ Time Frame: Up to 24 months ]
    Will use PRO CTCAE, EQ 5D, EORTC QLQ-ANL 27, FSFI, and IIEF questionnaires. The study will summarize and graph the distribution of scores for each instrument over time and analyze changes over time using mixed effects linear models.

  10. Time-Driven Activity-Based Costing (TDABC) [ Time Frame: At 12 weeks post-treatment ]
    The study will 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. Costs will be tabulated as either treatment or toxicity-management related.


Other Outcome Measures:
  1. Dose to pelvic bone marrow, bowel, bladder and genitalia [ Time Frame: Up to 12 weeks ]
    Will be compared LET-optimized IMPT, traditionally optimized IMPT and VMAT. Dosimetric studies will be performed.

  2. Rates of leukopenia, neutropenia and lymphopenia [ Time Frame: Up to 12 weeks ]
    Will compare the on-treatment blood count nadirs for patients treated with LET-optimized IMPT with matched historical controls treated with VMAT. Continuous variables will be compared using Wilcoxon-Rank Sum test and corresponding p-values will be reported.

  3. Levels of white blood cell counts, absolute neutrophil counts, and absolute lymphocyte counts [ Time Frame: Up to 12 weeks ]
    Will be correlated with dose to the pelvic bone marrow for patients treated with LET-optimized IMPT. Will use Spearman rank correlation coefficient to evaluate for correlation.

  4. Optional co-enrollment on study 2014-0543 [ Time Frame: Up to 12 weeks ]
    Will use descriptive statistics and graphical methods.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 =< 1.5 mg/dL (within 14 days prior to study registration)
  • Bilirubin =< 1.4 mg/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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03690921


Contacts
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Contact: Emma B. Holliday 713-563-2300 EBHolliday@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Emma B. Holliday    713-563-2300      
Principal Investigator: Emma B. Holliday         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Emma B Holliday M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03690921     History of Changes
Other Study ID Numbers: 2018-0420
NCI-2018-02040 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2018-0420 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: October 1, 2018    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Anus Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Cisplatin
Fluorouracil
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs