Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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)

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed Over 21 NCI SCCC-2002033 NCI-6301, 6301, NCT00077051

Objectives

Primary

1. 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.
2. Determine the safety and toxicity profile of cytochlor, tetrahydrouridine, and concurrent radiotherapy followed by radiotherapy alone in these patients.
3. Determine the percentage of cancer cells vs normal cells that incorporate cytochlor in the DNA of patients treated with this regimen.
4. Determine the percentage replacement of thymine by 5-chlorouracil in tumors vs normal tissue of patients treated with this regimen.

Secondary

1. Determine the tissue selectivity of this regimen in these patients.
2. 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.
3. Determine the pharmacokinetics of this regimen in these patients.

Entry 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

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

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/mm³
• WBC at least 3,000/mm³
• Platelet count greater than 100,000/mm³

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)

Expected Enrollment

A total of 3-18 patients will be accrued for this study within 2 years.

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.

Trial Contact Information

Trial Lead Organizations

University of Miami Sylvester Comprehensive Cancer Center - Miami

Luis Raez, MD, FACP, Protocol chair		Ph: 305-243-4909
May Abdel-Wahab, MD, PhD, Protocol co-chair		Ph: 305-243-4210 Email: mwahab@med.miami.edu

Registry Information
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
Trial Start Date		2004-04-01
Registered in ClinicalTrials.gov		NCT00077051
Date Submitted to PDQ		2004-01-07
Information Last Verified		2005-12-20

Back to Top