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) - Full Text View

Sponsor:	University of Miami Sylvester Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00077051

Purpose

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 I

Study Type:	Interventional
Study Design:	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:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Cisplatin Tetrahydrouridine

U.S. FDA Resources

Further study details as provided by University of Miami Sylvester Comprehensive Cancer Center:

Study Start Date:

April 2004

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.

Eligibility

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00077051

Locations

United States, Florida
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136

Sponsors and Collaborators

University of Miami Sylvester Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:	Luis E. Raez, MD, FACP	University of Miami Sylvester Comprehensive Cancer Center
Investigator:	May Abdel-Wahab, MD, PhD	University of Miami Sylvester Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Luis Raez, MD, University of Miami Sylvester Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00077051 History of Changes
Other Study ID Numbers:	EPROST-20020154, SCCC-2002033, NCI-6301
Study First Received:	February 10, 2004
Last Updated:	September 21, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Miami Sylvester Comprehensive Cancer Center:

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
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Cisplatin

Tetrahydrouridine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 13, 2012