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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Summary:

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 continu
    Sponsor: ECOG-ACRIN Cancer Research Group

    Current 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.


    Original Primary Outcome:

    Current Secondary Outcome:

    • 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 ]
      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.
    • 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 ]
      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.
    • 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 ]
      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).
    • 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 ]
      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.


    Original Secondary Outcome:

    Information By: Eastern Cooperative Oncology Group

    Dates:
    Date Received: April 19, 2006
    Date Started: January 2007
    Date Completion: May 2022
    Last Updated: May 18, 2017
    Last Verified: October 2016