Cytochlor and Tetrahydrouridine as Radiosensitizers and Cisplatin Combined With Radiation Therapy in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity (Mouth) or Oropharynx (Throat)
Condition: Head and Neck Cancer
MeSH terms: Carcinoma; Carcinoma, Squamous Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Radiosensitizing
      drugs, such as cytochlor and tetrahydrouridine, may make tumor cells more sensitive to
      radiation therapy. Drugs used in chemotherapy, such as cisplatin work in different ways to
      stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Combining radiosensitizers with chemotherapy and radiation therapy may kill more
      tumor cells.

      PURPOSE: This phase I trial is studying the side effects and best dose of cytochlor when
      given together with tetrahydrouridine, cisplatin and radiation therapy in treating patients
      with advanced squamous cell carcinoma of the oral cavity (mouth) or oropharynx (throat).
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the dose range of cytochlor to be used in phase II trials, based on safety,
           toxicity, and tissue selectivity, in patients with advanced squamous cell carcinoma of
           the oral cavity or oropharynx.

        -  Determine the safety and toxicity profile of cytochlor, tetrahydrouridine, and
           concurrent radiotherapy followed by radiotherapy alone in these patients.

        -  Determine the percentage of cancer cells vs normal cells that incorporate cytochlor in
           the DNA of patients treated with this regimen.

        -  Determine the percentage replacement of thymine by 5-chlorouracil in tumors vs normal
           tissue of patients treated with this regimen.

      Secondary

        -  Determine the tissue selectivity of this regimen in these patients.

        -  Determine the level of cytochlor and its metabolites within the serum and urine of these
           patients during combination treatment and before radiotherapy alone is initiated.

        -  Determine the pharmacokinetics of this regimen in these patients.

      OUTLINE: This is an open-label, dose-escalation study of cytochlor.

      Patients receive tetrahydrouridine IV over 5 minutes followed by cytochlor IV for 3 days on
      week 1 and 5 days a week on weeks 2-4 and cisplatin IV over 30-60 minutes once in weeks 2 and
      5. Patients also undergo radiotherapy 5 days a week during weeks 2-7. Treatment continues in
      the absence of disease progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of cytochlor until the maximum tolerated
      dose (MTD) is determined. The MTD is defined as the dose at which 1 of 3 or 3 of 6 patients
      experience dose-limiting toxicity.

      Patients are followed at 1 month, monthly for 3 months, every 3 months for up to 1 year,
      every 4 months for 1 year, every 6 months for 1 year, and then annually thereafter.

      PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within 2 years.
    

Intervention name(s): cisplatin; cytochlor; tetrahydrouridine; radiation therapy
Intervention type(s): Drug; Drug; Drug; Radiation
Intervention MeSH terms: Tetrahydrouridine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage III squamous cell carcinoma of the lip and oral cavity; stage III squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the oropharynx