Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer

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Brief Title

Cetuximab, Cisplatin, Fluorouracil, and Radiation Therapy in Treating Patients With Anal Cancer

Official Title

Phase II Trial of Cetuximab Plus Cisplatin, 5- Fluorouracil and Radiation in Immunocompetent Patients With Anal Carcinoma

Brief 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. 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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Local Failure Rate at 3 Years

Secondary Outcome

 3-year Overall Survival Rate

Condition

Anal Cancer

Intervention

cetuximab

Study Arms / Comparison Groups

 Arm I (closed to accrual as of 11/3/2008)
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

63

Start Date

January 2007

Completion Date

May 2022

Primary Completion Date

November 2015

Eligibility Criteria

        INCLUSION CRITERIA:

          -  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

          -  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)

        EXCLUSION CRITERIA:

          -  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

               -  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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Madhur K. Garg, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00316888

Organization ID

E3205

Secondary IDs

E3205

Responsible Party

Sponsor

Study Sponsor

ECOG-ACRIN Cancer Research Group

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Madhur K. Garg, MD, Study Chair, Montefiore Medical Center


Verification Date

October 2020