Combined Modality Therapy for Patients With With HIV and Stage I, Stage II, or Stage III Anal Cancer
Condition: Anal Cancer
MeSH terms: Anus Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: 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. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways.
      Some block the ability of tumor cells to grow and spread. Others find tumor cells and help
      kill them or carry tumor-killing substances to them. Radiation therapy uses high-energy
      x-rays to kill tumor cells. Giving cisplatin, fluorouracil, and cetuximab together with
      radiation therapy may kill more tumor cells.

      PURPOSE: This phase II trial is studying how well giving cisplatin, fluorouracil, and
      cetuximab together with radiation therapy works in treating patients with HIV and stage I,
      stage II, or stage III anal cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the 2-year local failure rate in patients with HIV-associated stage I-IIIB
           anal carcinoma treated with cisplatin, fluorouracil, cetuximab, and radiotherapy.

        -  Determine the objective response rate (complete and partial), progression-free survival,
           relapse-free survival, colostomy-free survival, overall survival, quality of life, and
           overall toxicity in patients treated with this regimen.

      Secondary

        -  Characterize the effect of this regimen on the underlying HIV condition by describing
           changes in viral load, CD4 counts, and the incidence of opportunistic illnesses,
           including the development of AIDS during and in the first year after treatment.

        -  Evaluate the effect of this regimen on anogenital human papilloma virus (HPV) infection
           and anal cytology.

      OUTLINE: This is an open-label, multicenter study.

      Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 35*, fluorouracil
      IV continuously on days 1-4 and 29-32, and cisplatin IV over 1 hour on days 1 and 29.
      Beginning on day 1, patients undergo concurrent radiotherapy to the primary tumor 5 days a
      week for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable
      toxicity.

      NOTE: *Patients receiving 7 weeks of radiotherapy also receive cetuximab on days 42 and 49.

      Quality of life is assessed at baseline, at the completion of study treatment, and then at
      months 3, 6, 12, 24, and 36.

      After completion of study treatment, patients are followed periodically for 5 years.

      PROJECTED ACCRUAL: A total of 47 patients will be accrued for this study.
    

Intervention name(s): cetuximab; cisplatin; fluorouracil; radiation therapy
Intervention type(s): Biological; Drug; Drug; Radiation
Intervention description(s): 400 mg/m2 IV Day -7 (1 week before the cycle 1, Day 1 cisplatin/5-FU and RT), then 250 mg/m2 IV Days 1, 8, 15, 22, 29, 36 and 43 (a minimum of 6 and a maximum of 8 doses of cetuximab will be administered, including the loading dose); 75 mg/m2 IV on Day 1 (cycle 1) and Day 29 (cycle 2); 1000 mg/m2/day by continuous intravenous infusion on Days 1-4 (cycle 1) and Days 29-32 (cycle 2); Irradiation to tumor site and inguinal nodes beginning on cycle 1, Day 1 cisplatin/5-FU (minimum 45.0 Gy [5 weeks if given on schedule and without interruption], maximum 54.0 Gy [6 weeks if given on schedule and without interruption). IMRT may be used at the discretion of the treating physician.
Other intervention name(s): Erbitux; Platinol; 5-FU; Adrucil; Carac; Efudex; Fluoroplex
Intervention MeSH terms: Fluorouracil; Cetuximab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I anal cancer; stage II anal cancer; stage IIIA anal cancer; stage IIIB anal cancer; squamous cell carcinoma of the anus; basaloid carcinoma of the anus; cloacogenic carcinoma of the anus