NCI ID NCI-2019-02259
NCT ID NCT04166318
CTEP ID EA2182
Primary Purpose TREATMENT
Anatomic Sites Anus
Minimum Age 18 Years
Maximum Age 999 Years
Gender BOTH
Lead Org ECOG-ACRIN Cancer Research Group
Principal Investigator Jennifer Anne Dorth
NCI Site View on ClinicalTrials.gov

Lower-Dose Chemoradiation in Treating Patients with Early-Stage Anal Cancer, the DECREASE Study

This phase II trial studies how well lower-dose chemotherapy plus radiation (chemoradiation) therapy works in comparison to standard-dose chemoradiation in treating patients with early-stage anal cancer. Drugs used in chemotherapy, such as mitomycin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Giving chemotherapy with radiation therapy may kill more tumor cells. This study may help doctors find out if lower-dose chemoradiation is as effective and has fewer side effects than standard-dose chemoradiation, which is the usual approach for treatment of this cancer type.

Eligibility

Inclusion Criterea

  • STEP 0 (PRE-REGISTRATION)
  • Patients must be English speaking to participate in the trial. (Please note that this requirement is due to the fact that the quality-of-life studies are mandatory and we currently do not have full translated versions of the questionnaires into other languages)
  • Patient must have histologically proven T1-2N0M0 invasive anal canal or anal margin squamous cell carcinoma with tumors measuring =< 4 cm. This may include tumors of non-keratinizing histology such as basaloid, transitional cell or cloacogenic histology. Measurable disease is not required
  • Patients who are status/post local excision or excisional biopsy procedure are eligible provided there was tumor involvement of the anal canal and/or anal verge prior to the reaction, if the margins were positive, and/or if the stage is T2N0 based on tumor size before the procedure. This means that patients with T1N0M0 anal margin squamous cell carcinoma who underwent surgical excision with negative margins and no involvement of the anal verge and/or anal canal are not eligible
  • Tumor size must be documented based on physical examination including digital rectal exam and/or anoscopy/proctoscopy within 4 weeks prior to Step 0 pre-registration
  • Patient’s human immunodeficiency virus (HIV) status must be known and documented at baseline * NOTE: For patients without a history of HIV infection, it is recommended (but not required) that updated HIV testing be performed within one year of study enrollment
  • Patients who are HIV-negative will be registered to Arm R. They must not have lymph nodes that are radiographically-concerning for cancer involvement using computed tomography (CT) and fludeoxyglucose F-18 (FDG) - positron emission tomography (PET)/CT-based criteria * NOTE: Patients who are HIV-negative and meet the below criteria may proceed directly to Step 1 Randomization * Patients will be considered to be lymph node (LN) positive and thereby not eligible in this study if the lymph nodes meet any of the following criteria: ** Mesorectal, presacral, internal iliac or obturator LN with: *** Short axis measuring > 5 mm based on CT/magnetic resonance imaging (MRI) OR *** Morphologic features of irregular border or central necrosis if assessed on MRI and LN measures > 3 mm OR *** FDG uptake > blood pool (Deauville 3-5) based on FDG-PET/CT or PET/MRI ** Internal Iliac and obturator LN with: *** Short-axis measuring > 7 mm based on CT/MRI OR *** Morphologic features of irregular border or central necrosis based on CT/MRI OR *** FDG uptake > blood pool (Deauville 3-5) based on FDG-PET/CT or PET/MRI ** External Iliac and common Iliac: *** Short-axis measuring > 10 mm based on CT/MRI OR *** Morphologic features of irregular border or central necrosis based on CT/MRI OR *** FDG uptake > blood pool (Deauville 3-5) based on FDG-PET/CT or PET/MRI * Inguinal LN (superficial and deep) meeting any of the following criteria will be ineligible unless an fine needle aspiration (FNA) is performed and resulting cytology is negative. ** Morphologic features of irregular border or central necrosis based on CT/MRI ** FDG uptake > liver (Deauville 4) based on FDG-PET/CT. ** Patients who are HIV-negative and have inguinal lymph nodes that do not meet the above criteria must undergo fine needle aspiration and have negative histology to be eligible
  • Patients who are HIV-positive will be registered to Arm S. They must meet the eligibility criteria below: * A CD4 count >= 200 * Imaging submitted to ECOG-ACRIN for central review for confirmation of no lymph node involvement * No history of acquired immunodeficiency syndrome (AIDS)-related complications within past year other than a history of low CD4+ T-cell count (> 200/mm^3) prior to initiation of combination antiretroviral therapy * Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the anal cancer * Patient MUST receive appropriate care and treatment for HIV infection, including antiretroviral medications when clinically indicated, and should be under the care of a physician experienced in HIV management. Patients will be eligible regardless of antiretroviral medication provided the regimen has been stable for at least 4 weeks
  • STEP 1 RANDOMIZATION
  • Patient must have met the eligibility criteria as outlined Step 0 Pre-registration
  • Patient must have Eastern Cooperative Oncology Group (ECOG) - American College of Radiology Imaging Network (ACRIN) performance status of 0-2
  • Patient must have no history of prior chemotherapy for this malignancy
  • Patients must not have undergone previous radiation to the pelvis such that overlapping radiation fields would be expected
  • Patient must not have had prior potentially curative surgery (i.e. abdominal-perineal resection) for carcinoma of the anus. However, patients who undergo local excision or excisional biopsy are eligible provided they meet inclusion criteria
  • Patients with T1N0M0 anal margin squamous cell carcinoma must not have undergone surgical excision with negative margins and no involvement of the anal verge and/or anal canal
  • Patient must not be receiving any other standard anti-cancer therapy or experimental agent concurrently with the study drugs
  • Patient must not have intercurrent illness including, but not limited to, ongoing or active infection or psychiatric/social situations that, in the judgement of the investigator, would limit compliance with study requirements
  • Patient must not have had significant cardiovascular disease including myocardial infarction, unstable angina, stroke, transient ischemic attack, symptomatic coronary artery disease, symptomatic congestive heart failure, or uncontrolled cardiac arrhythmia within 6 months of Step 1 randomization
  • Patient must not have a history of a different malignancy unless they have been disease-free for at least 2 years and are deemed by the investigator to be at low risk of recurrence * Exceptions to this rule are individuals with cervical cancer in situ, non-melanoma skin cancers, and colon polyps
  • Patient must not have active inflammatory bowel disease (patients requiring current medical interventions or who are symptomatic)
  • Patients must not have an active autoimmune or connective tissue disease that has required systemic treatment in the past two years (i.e., with the use of modifying agents, corticosteroids, or immunosuppressive drugs) Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patients who are on anti-coagulation with warfarin within 2 weeks prior to Step 1 randomization and are considering the use of capecitabine, must use an alternative anti-coagulant * NOTE: Low molecular weight heparin is permitted provided the patient’s prothrombin time (PT)/international normalized ratio (INR) is < 1.5
  • Patients who will receive capecitabine and are on Dilantin for a seizure disorder must have Dilantin levels checked weekly
  • Hemoglobin > 10 g/dL (within 2 weeks prior to Step 1 Randomization)
  • Platelets >= 100,000/mm^3 (within 2 weeks prior to Step 1 Randomization)
  • Absolute neutrophil count >= 1500/mm^3 (within 2 weeks prior to Step 1 Randomization)
  • Serum creatinine must be < 1.5 X upper limit of normal (ULN), or calculated creatinine clearance must be > 50 ml/min (within 2 weeks prior to Step 1 Randomization)
  • Total bilirubin must be < 2 X ULN (within 2 weeks prior to Step 1 Randomization)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 X institutional ULN (within 2 weeks prior to Step 1 Randomization)
  • Albumin >= 3.0 g/dL (within 2 weeks prior to Step 1 Randomization)
  • Women must not be pregnant or breast-feeding because the study treatment administered may cause harm to an unborn fetus or breastfeeding child. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to Step 1 Randomization to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Women of childbearing potential and sexually active males must be strongly advised to use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for at least 6 months after the completion of treatment

Exclusion Criterea


Participating Clinics

North Star Lodge Cancer Center at Yakima Valley Memorial Hospital


808 North 39th Avenue
Yakima, WA 98902
Map

509-574-3535
Memorial-ClinicalTrials@yvmh.org

Saint Mary's Regional Medical Center


235 West Sixth Street
Reno, NV 89503
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Medical Center


6450 Medical Center Street
Las Vegas, NV 89148-2405
Map

702-384-0013
research@sncrf.org

Kingman Regional Medical Center


3269 Stockton Hill Road
Kingman, AZ 86401
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Southeast


3980 South Eastern Avenue
Las Vegas, NV 89119
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Fort Apache


6160 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Vegas Tenaya


2851 North Tenaya Way
Suite 100 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Shadow


701 Shadow Lane
Suite 300 Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Fort Apache


6190 South Fort Apache Road
Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-San Martin


8285 West Arby Avenue
Suite 100 Las Vegas, NV 89113
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills


6850 North Durango Drive
Suite 120 Las Vegas, NV 89149
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Summerlin


655 North Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Summerlin Hospital Medical Center


657 Town Center Drive
Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

PCR Oncology


584 Camino Mercado
Arroyo Grande, CA 93420
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Tenaya


3150 North Tenaya Way
Suite 430 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Southeast Henderson


1505 Wigwam Parkway
Suite 130 Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

Las Vegas Cancer Center-Henderson


2904 West Horizon Ridge Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Henderson


52 North Pecos Road
Henderson, NV 89074
Map

702-384-0013
research@sncrf.org

GenesisCare USA - Las Vegas


3006 South Maryland Parkway
Suite 100 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Tenaya


2851 North Tenaya Way
Suite 101 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Henderson


10001 South Eastern Avenue
Suite 108 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Ann M Wierman MD LTD


3150 Tenaya Way
Suite 200 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada-Horizon Ridge


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at MountainView


3150 North Tenaya Way
Suite 510 Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

University Cancer Center


3131 La Canada Street
Suite 231 Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada


6827 West Tropicana Avenue
Suite 110 Las Vegas, NV 89103
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Charleston


2300 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013

Desert West Surgery


1111 Shadow Lane
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Hope Cancer Care of Nevada-Pahrump


2340 East Calvada Boulevard
Suite 7 Pahrump, NV 89048
Map

702-384-0013
research@sncrf.org

OptumCare Cancer Care at Seven Hills


3175 Saint Rose Parkway
Suite 200 Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Carson Tahoe Regional Medical Center


1535 Medical Parkway
Pharmacy Suite C Carson City, NV 89703
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Northwest


7445 Peak Drive
Las Vegas, NV 89128
Map

702-384-0013
research@sncrf.org

Radiation Oncology Centers of Nevada Central


624 South Tonopah Drive
Las Vegas, NV 89106
Map

702-384-0013
research@sncrf.org

Radiation Oncology Associates


6630 B South McCarran
Suite 18 Reno, NV 89509
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada


9280 West Sunset Road
Suite 100 Las Vegas, NV 89148
Map

702-384-0013
research@sncrf.org

Alliance for Childhood Diseases/Cure 4 the Kids Foundation


One Breakthrough Way
Las Vegas, NV 89135
Map

702-384-0013
research@sncrf.org

Cancer and Blood Specialists-Henderson


2460 West Horizon Ridge Parkway
Henderson, NV 89052
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Central Valley


3730 South Eastern Avenue
Las Vegas, NV 89169
Map

702-384-0013
research@sncrf.org

HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway


3006 South Maryland Parkway
Suite 205 Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

University Medical Center of Southern Nevada


1800 West Charleston Boulevard
Las Vegas, NV 89102
Map

702-384-0013
research@sncrf.org

Renown Regional Medical Center


1155 Mill Street
Reno, NV 89502
Map

702-384-0013
research@sncrf.org

Sunrise Hospital and Medical Center


3186 South Maryland Parkway
Las Vegas, NV 89109
Map

702-384-0013
research@sncrf.org

Comprehensive Cancer Centers of Nevada - Town Center


653 North Town Center Drive
Suite 402 Las Vegas, NV 89144
Map

702-384-0013
research@sncrf.org

Las Vegas Urology - Pecos


9053 South Pecos Road
Suite 2900 Las Vegas, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Cathedral Rock


7200 Cathedral Rock Drive
Suites 180 and 210 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Urology - Pebble


8915 South Pecos Road
Suite 19A Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Prostate Cancer Center


7150 West Sunset Road
Suite 100 Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Northwest


3150 North Tenaya Way
Suite 165 Las Vegas, NV 89128
Map


research@sncrf.org

Las Vegas Urology - Sunset


7150 West Sunset Road
Suite 201A and 202B Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Southwest


8410 West Warm Springs Road
Suite 10 Las Vegas, NV 89113
Map


research@sncrf.org

Urology Specialists of Nevada - Central


2010 Wellness Way
Suite 200 Las Vegas, NV 89106
Map


research@sncrf.org

Urology Specialists of Nevada - Green Valley


58 North Pecos Road
Henderson, NV 89074
Map


research@sncrf.org

Las Vegas Urology - Green Valley


1701 North Green Valley Parkway
Suite 10C Henderson, NV 89074
Map


research@sncrf.org

Valley Medical Center


400 South 43rd Street
Renton, WA 98055
Map

425-228-3440
research@valleymed.org