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)

This study has been completed.
Information provided by (Responsible Party):
University of Miami Identifier:
First received: February 10, 2004
Last updated: August 13, 2013
Last verified: August 2013

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).

Condition Intervention Phase
Head and Neck Cancer
Drug: cisplatin
Drug: cytochlor
Drug: tetrahydrouridine
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Translational Phase I Trial of Escalating Doses of 5-Chloro-2'-Deoxycytidine (CldC) With a Fixed Dose of Tetrahydrouridine Combined With a Fixed Dose of Cisplatin Comcomitant With Definitive Radiation in Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity and Oropharynx

Resource links provided by NLM:

Further study details as provided by University of Miami:

Enrollment: 1
Study Start Date: April 2004
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: cisplatin Drug: cytochlor Drug: tetrahydrouridine Radiation: radiation therapy

Detailed Description:



  • 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.


  • 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.


Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity or oropharynx

    • Stage III disease not eligible for surgery
    • Stage IV disease allowed if patient is not eligible for chemotherapy or refused chemotherapy
    • No distant metastasis
  • Previously untreated disease
  • No osteoradionecrosis in patients with tumors involving the maxilla
  • Tumor tissue/normal adjacent tissue (T/N) ratio for dC kinase and dCMP deaminase greater than 2.5



  • Over 21

Performance status

  • Karnofsky 80-100% OR
  • ECOG 0-1

Life expectancy

  • More than 6 months


  • Absolute neutrophil count greater than 1,500/mm^3
  • WBC at least 3,000/mm^3
  • Platelet count greater than 100,000/mm^3


  • AST/ALT less than 2.5 times upper limit of normal
  • Bilirubin normal


  • Creatinine normal OR
  • Creatinine clearance greater than 60 mL/min


  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • No impending carotid rupture


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study treatment
  • HIV negative
  • No other concurrent uncontrolled illness
  • No active or ongoing infection
  • No alcohol dependence
  • No psychiatric illness or social situation that would preclude study compliance
  • No other malignancy within the past 3 years except low-risk, non-melanomatous skin cancer, carcinoma in situ (e.g., breast, cervix, or bladder), or stage T1-2, low-to-moderate grade prostate cancer (Gleason score no greater than 7)


Biologic therapy

  • No concurrent immunotherapy


  • See Disease Characteristics
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent hormonal therapy except contraceptives or replacement steroids


  • Not specified


  • See Disease Characteristics


  • No prior therapy for head and neck cancer
  • No other concurrent experimental medications
  • No other concurrent anticancer therapy
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  Contacts and Locations
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Please refer to this study by its identifier: NCT00077051

United States, Florida
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Study Chair: Luis E. Raez, MD, FACP University of Miami
Principal Investigator: May Abdel-Wahab, MD, PhD University of Miami
  More Information

Additional Information:
No publications provided

Responsible Party: University of Miami Identifier: NCT00077051     History of Changes
Other Study ID Numbers: UMIAMI-20020154, SCCC-2002033, NCI-6301
Study First Received: February 10, 2004
Last Updated: August 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
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

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action processed this record on July 24, 2014