Anal CancerPhase 2NCT00316888
Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer
A Phase 2 study testing cetuximab, cisplatin and fluorouracil in people with Anal Cancer, run by ECOG-ACRIN Cancer Research Group at 125 sites in United States.
Trial summary
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anal Cancer
- What is being tested?
- cetuximab, cisplatin and fluorouracil
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 125 sitesUnited States
- Study dates
- 28 Feb 2007to 17 Aug 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed anal canal or perianal (anal margin) squamous cell carcinoma
- Stage I-IIIB (closed to accrual as of 11/3/2008)
- Stage II (T3, N0 only), IIIA, or IIIB
- Tumors of nonkeratinizing histology, such as basaloid, transitional cell, or cloacogenic histology, allowed
- No well-differentiated stage I anal margin cancer
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
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- Hemoglobin ≥ 10 g/dL
- Platelet count ≥ 100,000/mm^3
- Absolute neutrophil count > 1,500/mm^3
- Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 60 mL/min
- Bilirubin ≤ 2 times ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
- No other malignancies except nonmelanomatous skin cancer
- Prior malignancies must be in remission for ≥ 5 years
- Patients with a known risk factor for human immunodeficiency virus (HIV) infection must undergo HIV testing within 90 days before study entry AND must be HIV negative by antibody detection, culture, or quantitative assay of plasma HIV ribonucleic acid (RNA)
Who cannot join
- Presence of the following conditions within the past 6 months:
- Active infection
- Uncontrolled diabetes
- New York Heart Association class II-IV congestive heart failure
- Cerebrovascular accident
- Transient ischemic attack
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- Uncontrolled hypertension
- Unstable angina
- Myocardial infarction
- History of rheumatic disorders, irritable bowel syndrome, or inflammatory bowel disease
- Known HIV positivity
- Known risk factors for HIV infection
- Prior radiotherapy or chemotherapy for this malignancy
- Prior pelvic radiotherapy
- Prior potentially curative surgery (i.e., abdominal or peritoneal resection) for anal cancer
- Pregnant or nursing
Trial locations and contacts
125 sites in 1 country.
125 sites in 1 country
United States125 sites
Hickman Cancer Center at Bixby Medical Center
Adrian, Michigan, 49221
Greater Baltimore Medical Center Cancer Center
Baltimore, Maryland, 21204
Mary Bird Perkins Cancer Center - Baton Rouge
Baton Rouge, Louisiana, 70809
Wood County Oncology Center
Bowling Green, Ohio, 43402
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Cedar Rapids Oncology Associates
Cedar Rapids, Iowa, 52403
Mercy Regional Cancer Center at Mercy Medical Center
Cedar Rapids, Iowa, 52403
Cancer Center of Kansas, PA - Chanute
Chanute, Kansas, 66720
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
Hematology and Oncology Associates
Chicago, Illinois, 60611
Adena Regional Medical Center
Chillicothe, Ohio, 45601
Marshfield Clinic - Chippewa Center
Chippewa Falls, Wisconsin, 54729
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, 43214-3998
CCOP - Columbus
Columbus, Ohio, 43215
Grant Medical Center Cancer Care
Columbus, Ohio, 43215
Mount Carmel Health - West Hospital
Columbus, Ohio, 43222
Doctors Hospital at Ohio Health
Columbus, Ohio, 43228
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, 55433
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, 62526
Grady Memorial Hospital
Delaware, Ohio, 43015
Cancer Center of Kansas, PA - Dodge City
Dodge City, Kansas, 67801
Marshfield Clinic Cancer Care at Regional Cancer Center
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Cancer Center of Kansas, PA - El Dorado
El Dorado, Kansas, 67042
Community Cancer Center
Elyria, Ohio, 44035
Hematology Oncology Center
Elyria, Ohio, 44035
Poudre Valley Hospital
Fort Collins, Colorado, 80524
Front Range Cancer Specialists
Fort Collins, Colorado, 80528
Cancer Center of Kansas - Fort Scott
Fort Scott, Kansas, 66701
Fredericksburg Oncology, Incorporated
Fredericksburg, Virginia, 22401
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, 55432
Kellogg Cancer Care Center
Highland Park, Illinois, 60035
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350
Cancer Center of Kansas-Independence
Independence, Kansas, 67301
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202-5289
William N. Wishard Memorial Hospital
Indianapolis, Indiana, 46202
UW Cancer Center Johnson Creek
Johnson Creek, Wisconsin, 53038
Borgess Medical Center
Kalamazoo, Michigan, 49001
West Michigan Cancer Center
Kalamazoo, Michigan, 49007-3731
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Provena St. Mary's Regional Cancer Center - Kankakee
Kankakee, Illinois, 60901
Cancer Center of Kansas, PA - Kingman
Kingman, Kansas, 67068
Fairfield Medical Center
Lancaster, Ohio, 43130
Lawrence Memorial Hospital
Lawrence, Kansas, 66044
Cancer Center of Kansas, PA - Liberal
Liberal, Kansas, 67901
North Shore Oncology and Hematology Associates, Limited - Libertyville
Libertyville, Illinois, 60048
Lima Memorial Hospital
Lima, Ohio, 45804
Cancer Resource Center - Lincoln
Lincoln, Nebraska, 68510
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, 53792-6164
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, 55109
Minnesota Oncology - Maplewood
Maplewood, Minnesota, 55109
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, 45750
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, 54449
Northwest Ohio Oncology Center
Maumee, Ohio, 43537-1839
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, 55415
Marshfield Clinic - Lakeland Center
Minocqua, Wisconsin, 54548
Community Cancer Center of Monroe
Monroe, Michigan, 48162
Mercy Memorial Hospital - Monroe
Monroe, Michigan, 48162
Carol G. Simon Cancer Center at Morristown Memorial Hospital
Morristown, New Jersey, 07962
Knox Community Hospital
Mount Vernon, Ohio, 43050
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, 70112
Medical Center of Louisiana - New Orleans
New Orleans, Louisiana, 70112
NYU Cancer Institute at New York University Medical Center
New York, New York, 10016
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, 43055
Cancer Center of Kansas, PA - Newton
Newton, Kansas, 67114
Cancer Care and Hematology Specialists of Chicagoland - Niles
Niles, Illinois, 60714
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106
Immanuel Medical Center
Omaha, Nebraska, 68122
Alegant Health Cancer Center at Bergan Mercy Medical Center
Omaha, Nebraska, 68124
Lakeside Hospital
Omaha, Nebraska, 68130
Creighton University Medical Center
Omaha, Nebraska, 68131-2197
St. Charles Mercy Hospital
Oregon, Ohio, 43616
Toledo Clinic - Oregon
Oregon, Ohio, 43616
Cancer Center of Kansas, PA - Parsons
Parsons, Kansas, 67357
Joan Karnell Cancer Center at Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, 19111-2497
Southern Ohio Medical Center Cancer Center
Portsmouth, Ohio, 45662
Cancer Center of Kansas, PA - Pratt
Pratt, Kansas, 67124
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, 54501
Marshfield Clinic - Indianhead Center
Rice Lake, Wisconsin, 54868
Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, 55422-2900
Swedish-American Regional Cancer Center
Rockford, Illinois, 61104-2315
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, 55416
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Cancer Center of Kansas, PA - Salina
Salina, Kansas, 67401
Hematology and Oncology Associates of Northeastern Pennsylvania
Scranton, Pennsylvania, 18510
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, 55379
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101
Mercy Medical Center - Sioux City
Sioux City, Iowa, 51102
St. Luke's Regional Medical Center
Sioux City, Iowa, 51104
Hematology Oncology Associates - Skokie
Skokie, Illinois, 60076
Community Hospital of Springfield and Clark County
Springfield, Ohio, 45505
Stanford Cancer Center
Stanford, California, 94305-5824
Marshfield Clinic at Saint Michael's Hospital
Stevens Point, Wisconsin, 54481
Lakeview Hospital
Stillwater, Minnesota, 55082
Overlook Hospital
Summit, New Jersey, 07902
Flower Hospital Cancer Center
Sylvania, Ohio, 43560
Albert Einstein Cancer Center at Albert Einstein College of Medicine
The Bronx, New York, 10461
Mercy Hospital of Tiffin
Tiffin, Ohio, 44883
Toledo Hospital
Toledo, Ohio, 43606
St. Vincent Mercy Medical Center
Toledo, Ohio, 43608
Medical University of Ohio Cancer Center
Toledo, Ohio, 43614
CCOP - Toledo Community Hospital
Toledo, Ohio, 43617
St. Anne Mercy Hospital
Toledo, Ohio, 43623
Toledo Clinic, Incorporated - Main Clinic
Toledo, Ohio, 43623
CCOP - Carle Cancer Center
Urbana, Illinois, 61801
Ridgeview Medical Center
Waconia, Minnesota, 55387
Marshfield Clinic - Wausau Center
Wausau, Wisconsin, 54401
Fulton County Health Center
Wauseon, Ohio, 43567
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, 67152
Marshfield Clinic - Weston Center
Weston, Wisconsin, 54476
Associates in Womens Health, PA - North Review
Wichita, Kansas, 67208
Cancer Center of Kansas, PA - Medical Arts Tower
Wichita, Kansas, 67208
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, 67214
CCOP - Wichita
Wichita, Kansas, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, 67214
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, 56201
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, 67156
Marshfield Clinic - Wisconsin Rapids Center
Wisconsin Rapids, Wisconsin, 54494
Minnesota Oncology - Woodbury
Woodbury, Minnesota, 55125
Genesis - Good Samaritan Hospital
Zanesville, Ohio, 43701
About this study
Official title: Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cetuximab may help cisplatin and fluorouracil work better by making tumor cells more sensitive to the drugs. It may also make tumor cells more sensitive to radiation therapy. Giving cetuximab together with chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin, fluorouracil, and radiation therapy works in treating immunocompetent patients with stage I (closed to accrual as of 11/3/2008), stage II, (some stage II closed to accrual as of 11/3/2008) or stage III anal cancer.
Read the detailed description
OBJECTIVES:
Primary Objective:
- Determine whether the addition of cetuximab to combined modality therapy (CMT) comprising cisplatin, fluorouracil, and radiotherapy reduces the local failure rate by ≥ 50% at 3 years (compared with historical data) in immunocompetent patients with stage I-III invasive anal carcinoma.
Secondary Objectives:
- Determine objective response rate (complete and partial), progression-free survival, colostomy-free survival, and overall survival.
- Determine the overall toxicity of concurrent cisplatin, fluorouracil, and radiation therapy combined with cetuximab.
Exploratory Objectives:
- Evaluate the effect of cetuximab and CMT on anogenital herpes papilloma virus (HPV) infection and anal cytology.
- Evaluate whether moderate to strong expression of epidermal growth factor receptor, Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and P-Akt (as determined by immunohistochemistry) is associated with an increased risk of local failure.
OUTLINE: This is a multicenter study with two sequential arms. Arm I was closed to accrual as of 11/3/2008, and arm II opened to accrual on 8/18/2009. Patients are assigned to 1 of the 2 treatment arms.
- Arm I (closed to accrual as of 11/3/2008): Patients receive cisplatin intravenously (IV) over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57.
- Arm II (open to accrual on 8/18/2009): Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 8 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8.
After completion of study treatment, patients are followed periodically for up to 10 years.
PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.
- Conditions
- Anal Cancer
- Being tested
- cetuximab, cisplatin, fluorouracil, radiotherapy
- Keywords
- squamous cell carcinoma of the anus, stage I anal cancer, stage II anal cancer, stage IIIA anal cancer, stage IIIB anal cancer, basaloid carcinoma of the anus, cloacogenic carcinoma of the anus
- Medical subject headings
- Anus Neoplasms, Anal Canal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabBiological
Also called Erbitux
Given IV
cisplatinDrug
Also called Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II), Platinol, Platinol-AQ, cis-platinum
Given IV
fluorouracilDrug
Also called 5-Fluorouracil, 5-FU, Adrucil, Efudex
Given IV
radiotherapyRadiation
Also called radiation therapy
Given once daily 5 days a week for 5 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm I (closed to accrual as of 11/3/2008) | Experimental | Patients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Biological: cetuximab; Drug: cisplatin; Drug: fluorouracil; Radiation: radiotherapy |
| Arm II (open to accrual on 8/18/2009) | Experimental | Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. Receives: Biological: cetuximab; Drug: cisplatin; Drug: fluorouracil; Radiation: radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local Failure Rate at 3 Years
Local failure was defined as progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes after completion of protocol therapy, or progression during protocol therapy. Lost to follow-up and death (regardless of cause of death) prior to 3 years were also considered as local failures. For the calculation of local failure rate at 3 years, patients were classified into two groups (ie, coded as binary variable): failure (patients with local failure events prior to 3 years) vs. no failure (patients who still alive and had no local failure at 3 years). The binomial proportion and its exact two-sided 80% confidence interval (CI) were used to estimate it.
Measured: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Secondary outcomes (4)
3-year Overall Survival Rate
Overall survival (OS) is defined as time from registration to death from any cause. Patients alive are censored at the last contact date. Kaplan-Meier method was used to estimate the 3-year OS rate.
Measured: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
3-year Progression-free Survival Rate
Progression-free survival (PFS) was defined as time from registration to disease progression, relapse or death (whichever occurred first), censoring cases without PFS events at the date of last disease assessment documenting the patient was free of progression/relapse. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the 3-year PFS rate.
Measured: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Objective Response Rate
Objective response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all eligible and treated patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).
Measured: Tumor assessments were made at baseline, within 4 weeks of the completion of protocol treatment, then every 6 months if patient was 1-4 years from registration, yearly if patient was 5-10 years from registration until progression/relapse using the RECIST
3-year Colostomy-free Survival Rate
Colostomy-free survival was defined as time from registration until time of colostomy or death without colostomy, censoring cases without colostomy at the data of last disease assessment documenting the patient was free of colostomy. Kaplan-Meier method was used to estimate the 3-year colostomy-free survival rate.
Measured: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2006 (estimated)
- Study start28 Feb 2007
- Primary completionNov 2015
- Study completion17 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anal CancerStudies of the same condition, open and under way.
- More trials run by ECOG-ACRIN Cancer Research GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- ECOG-ACRIN Cancer Research Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Madhur K. Garg, MD, Study chair, Montefiore Medical CenterJoseph A. Sparano, MD, Study chair, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00316888
- Sponsor's protocol ID
- E3205
- Other IDs
- E3205, U10CA023318, CDR0000470269
- Status last verified
- Jun 2023
- First submitted
- 19 Apr 2006
- Last updated
- 29 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Publications
Garg M, Lee JY, Kachnic LA, et al.: Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): safety and preliminary efficacy results. [Abstract] J Clin Oncol 30 (Suppl 15): A-4030, 2012.
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma
- ClinicalTrials.gov ID
- NCT00316888
- Acronym / sponsor ID
- E3205
- Conditions
- Anal Cancer
- Keywords
- squamous cell carcinoma of the anus, stage I anal cancer, stage II anal cancer, stage IIIA anal cancer, stage IIIB anal cancer, basaloid carcinoma of the anus, cloacogenic carcinoma of the anus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- ECOG-ACRIN Cancer Research GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 28 Feb 2007 (actual)
- Primary completion
- Nov 2015 (actual)
- Study completion
- 17 Aug 2021 (actual)
- First posted
- 21 Apr 2006 (estimated)
- Results
- Posted 29 Aug 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Cetuximab may help cisplatin and fluorouracil work better by making tumor cells more sensitive to the drugs. It may also make tumor cells more sensitive to radiation therapy. Giving cetuximab together with chemotherapy and radiation therapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin, fluorouracil, and radiation therapy works in treating immunocompetent patients with stage I (closed to accrual as of 11/3/2008), stage II, (some stage II closed to accrual as of 11/3/2008) or stage III anal cancer.
Detailed description
OBJECTIVES:
Primary Objective:
- Determine whether the addition of cetuximab to combined modality therapy (CMT) comprising cisplatin, fluorouracil, and radiotherapy reduces the local failure rate by ≥ 50% at 3 years (compared with historical data) in immunocompetent patients with stage I-III invasive anal carcinoma.
Secondary Objectives:
- Determine objective response rate (complete and partial), progression-free survival, colostomy-free survival, and overall survival.
- Determine the overall toxicity of concurrent cisplatin, fluorouracil, and radiation therapy combined with cetuximab.
Exploratory Objectives:
- Evaluate the effect of cetuximab and CMT on anogenital herpes papilloma virus (HPV) infection and anal cytology.
- Evaluate whether moderate to strong expression of epidermal growth factor receptor, Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and P-Akt (as determined by immunohistochemistry) is associated with an increased risk of local failure.
OUTLINE: This is a multicenter study with two sequential arms. Arm I was closed to accrual as of 11/3/2008, and arm II opened to accrual on 8/18/2009. Patients are assigned to 1 of the 2 treatment arms.
- Arm I (closed to accrual as of 11/3/2008): Patients receive cisplatin intravenously (IV) over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57.
- Arm II (open to accrual on 8/18/2009): Patients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 8 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8.
After completion of study treatment, patients are followed periodically for up to 10 years.
PROJECTED ACCRUAL: A total of 62 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (closed to accrual as of 11/3/2008) | Experimental | Biological: cetuximab, Drug: cisplatin, Drug: fluorouracil, Radiation: radiotherapyPatients receive cisplatin IV over 60 minutes on days 1, 29, 57, and 85 and fluorouracil IV continuously over 96 hours on days 1-4, 29-32, 57-60, and 85-88. Patients also receive cetuximab IV over 120 minutes on day 50 and then IV over 60 minutes on days 57, 64, 71, 78, 85, 92, and 99 and undergo radiotherapy once daily 5 days a week for 5 weeks, beginning on day 57. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Arm II (open to accrual on 8/18/2009) | Experimental | Biological: cetuximab, Drug: cisplatin, Drug: fluorouracil, Radiation: radiotherapyPatients receive cetuximab IV over 120 minutes on day 1 and then IV over 60 minutes on days 8, 15, 22, 29, 36, 43, and 50. Patients also receive cisplatin IV over 60 minutes on days 1 and 36, fluorouracil IV continuously over 96 hours on days 8-11 and 36-39, and undergo radiotherapy once daily 5 days a week for 5 weeks beginning on day 8. Treatment continues in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed anal canal or perianal (anal margin) squamous cell carcinoma
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Hemoglobin ≥ 10 g/dL
- Platelet count ≥ 100,000/mm^3
- Absolute neutrophil count > 1,500/mm^3
Key exclusion criteria (16 listed)
- Presence of the following conditions within the past 6 months:
- History of rheumatic disorders, irritable bowel syndrome, or inflammatory bowel disease
- Known HIV positivity
- Known risk factors for HIV infection
- Prior radiotherapy or chemotherapy for this malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cetuximabAlso: ErbituxGiven IV | Biological | Arm I (closed to accrual as of 11/3/2008), Arm II (open to accrual on 8/18/2009) |
| cisplatinAlso: Cis-diaminedichloroplatinum Cis-diaminedichloroplatinum (II), Platinol, Platinol-AQ, cis-platinumGiven IV | Drug | Arm I (closed to accrual as of 11/3/2008), Arm II (open to accrual on 8/18/2009) |
| fluorouracilAlso: 5-Fluorouracil, 5-FU, Adrucil, EfudexGiven IV | Drug | Arm I (closed to accrual as of 11/3/2008), Arm II (open to accrual on 8/18/2009) |
| radiotherapyAlso: radiation therapyGiven once daily 5 days a week for 5 weeks | Radiation | Arm I (closed to accrual as of 11/3/2008), Arm II (open to accrual on 8/18/2009) |
Primary outcome
Local Failure Rate at 3 Years
Time frame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Local failure was defined as progression/relapse of disease in the anal canal and/or regional organs and/or regional lymph nodes after completion of protocol therapy, or progression during protocol therapy. Lost to follow-up and death (regardless of cause of death) prior to 3 years were also considered as local failures. For the calculation of local failure rate at 3 years, patients were classified into two groups (ie, coded as binary variable): failure (patients with local failure events prior to 3 years) vs. no failure (patients who still alive and had no local failure at 3 years). The binomial proportion and its exact two-sided 80% confidence interval (CI) were used to estimate it.
4 secondary outcomes
3-year Overall Survival Rate
Time frame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
3-year Progression-free Survival Rate
Time frame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Objective Response Rate
Time frame: Tumor assessments were made at baseline, within 4 weeks of the completion of protocol treatment, then every 6 months if patient was 1-4 years from registration, yearly if patient was 5-10 years from registration until progression/relapse using the RECIST
3-year Colostomy-free Survival Rate
Time frame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundGarg M, Lee JY, Kachnic LA, et al.: Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil (5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIV-positive (AMC045) patients with squamous cell carcinoma of the anal canal (SCAC): safety and preliminary efficacy results. [Abstract] J Clin Oncol 30 (Suppl 15): A-4030, 2012.
- Individual participant dataSharing planned: Yes. Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Madhur K. Garg, MD study chair
Montefiore Medical Center
Joseph A. Sparano, MD study chair
Montefiore Medical Center
125 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab, cisplatin and fluorouracil in people with Anal Cancer, run by ECOG-ACRIN Cancer Research Group at 125 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 125 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local Failure Rate at 3 Years (time frame: assessed every 3 months for patients within 2 years of registration, then every 6 months for patients in year 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00316888, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2023.