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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)

Primary Purpose

Head and Neck Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
cisplatin
cytochlor
tetrahydrouridine
radiation therapy
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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

Eligibility Criteria

21 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Miami Sylvester Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm

Arm Description

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
February 10, 2004
Last Updated
December 14, 2016
Sponsor
University of Miami
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00077051
Brief 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)
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 Concomitant With Definitive Radiation in Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity and Oropharynx
Study Type
Interventional

2. Study Status

Record Verification Date
December 2016
Overall Recruitment Status
Completed
Study Start Date
April 2004 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
July 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Miami
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Arm
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
cisplatin
Intervention Type
Drug
Intervention Name(s)
cytochlor
Intervention Type
Drug
Intervention Name(s)
tetrahydrouridine
Intervention Type
Radiation
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Luis E. Raez, MD, FACP
Organizational Affiliation
University of Miami Sylvester Comprehensive Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
May Abdel-Wahab, MD, PhD
Organizational Affiliation
University of Miami Sylvester Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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)

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