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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


Phase 1
21 Years
N/A
Not Enrolling
Both
Head and Neck Cancer

Thank you

Trial Information

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


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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

Age

- Over 21

Performance status

- Karnofsky 80-100% OR

- ECOG 0-1

Life expectancy

- More than 6 months

Hematopoietic

- Absolute neutrophil count greater than 1,500/mm^3

- WBC at least 3,000/mm^3

- Platelet count greater than 100,000/mm^3

Hepatic

- AST/ALT less than 2.5 times upper limit of normal

- Bilirubin normal

Renal

- Creatinine normal OR

- Creatinine clearance greater than 60 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No impending carotid rupture

Other

- 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)

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent immunotherapy

Chemotherapy

- See Disease Characteristics

- No other concurrent chemotherapy

Endocrine therapy

- No concurrent hormonal therapy except contraceptives or replacement steroids

Radiotherapy

- Not specified

Surgery

- See Disease Characteristics

Other

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Luis E. Raez, MD, FACP

Investigator Role:

Study Chair

Investigator Affiliation:

University of Miami Sylvester Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

EPROST-20020154

NCT ID:

NCT00077051

Start Date:

April 2004

Completion Date:

July 2007

Related Keywords:

  • Head and Neck Cancer
  • 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
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

University of Miami Sylvester Comprehensive Cancer CenterMiami, Florida  33136