Cytochlor, Tetrahydrouridine, and External-Beam Radiation Therapy in Treating Patients With Cancer That Has Spread to the Brain

NCT00521183 | Completed Phase 1 DMC

• 3 other identifiers: 20057104SCCC-2005097WIRB-20051340
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs, such as cytochlor and tetrahydrouridine, may make tumor cells more sensitive to radiation therapy. PURPOSE: This phase I trial is studying the side effects and best dose of cytochlor when given together with tetrahydrouridine and external-beam radiation therapy in treating patients with cancer that has spread to the brain.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult tumors metastatic to brain

Outcome Measures

Primary Outcomes (2)

• To establish a dose range of CldC for further clinical studies (Phase II clinical trials) based on safety and toxicity.

  2 Years

• b) Establish the safety and toxicity profile of CldC+ H4U when given in combination with RT for 2 weeks following treatment with the drug alone for 3 days in the week prior to the combined treatment.

  Duration of study treatment

Secondary Outcomes (3)

• a) Determine the effectiveness of H4U to inhibit systemic cytidine deaminase (CD) during the course of treatment with CldC + H4U.

  At protocol specified timepoints during treatment

• Cytochlor and metabolite levels in serum at weeks 1, 2, and 3

  Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment

• Cytochlor and metabolite levels in urine at weeks 1, 2, and 3

  Pharmacokinetic sampling at protocol-specified timepoints during duration of treatment

Study Arms (1)

CldC + H4U

EXPERIMENTAL

Drug: Cytochlor; Drug: Tetrahydrouridine; Radiation: Radiation Therapy

Interventions

Cytochlor DRUG

The study's starting dose of CldC is 50 mg/m2/day. The dose of CldC will be escalated / de-escalated for patients. Patients will receive CldC+H4U on 3 days (Wed, Thr, Fri) in week 1, which precedes the initiation of radiation therapy. Patients will receive H4U and CldC IV by bolus infusion. Treatment with CldC+H4U will then continue for 5 days (Mon-Fri) during each of weeks 2 and 3, and will be accompanied by radiation therapy at 3 Gy/fraction initiated 3-4 h after bolus infusion of CldC+H4U. Treatment with CldC+H4U and radiation will then stop at the end of week 3.

Also known as: CldC, CDC

CldC + H4U

Tetrahydrouridine DRUG

A fixed dose of H4U at 720 mg/m2/day will be used, regardless of the dose of CldC administered. H4U will be delivered by an IV bolus infusion over a period of 5 minutes, followed 5 minutes later by an IV bolus infusion of CldC. Patients will receive CldC+H4U on 3 days (Wed, Thr, Fri) in week 1, which precedes the initiation of radiation therapy. Patients will receive H4U and CldC IV by bolus infusion. Treatment with CldC+H4U will then continue for 5 days (Mon-Fri) during each of weeks 2 and 3, and will be accompanied by radiation therapy at 3 Gy/fraction initiated 3-4 h after bolus infusion of CldC+H4U. Treatment with CldC+H4U and radiation will then stop at the end of week 3.

Also known as: THU, H4U

CldC + H4U

Radiation Therapy RADIATION

One treatment of 3 Gy will be given daily 5 days per week (10 fractions) for a total of 30 Gy over two weeks.

CldC + H4U

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Karnofsky performance status (PS) 70-100% or ECOG PS 0-1
• Leukocytes ≥ 3,000/µL
• Absolute neutrophil count \> 1,500/µL
• Platelet count \> 100,000/µL
• Total bilirubin normal
• AST and ALT \< 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance \> 60 mL/min
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to, any of the following:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or lactating
• Alcohol dependence
• PRIOR CONCURRENT THERAPY:
• No prior radiotherapy to the brain
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent chemotherapy, immunotherapy, hormonal therapy (excluding contraceptives and replacement steroids), or other experimental medication
• No other concurrent anticancer therapy outside the protocol
• Systemic therapy one month before or after brain radiotherapy is allowed
• No concurrent heparin or coumadin

Sponsors & Collaborators

• Brian Lally: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Brain Neoplasms

Interventions

Centers for Disease Control and Prevention, U.S.; Tetrahydrouridine; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

United States Public Health Service; United States Dept. of Health and Human Services; United States Government Agencies; Federal Government; Government; Organizations; Health Care Economics and Organizations; Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Therapeutics

Study Officials

• Fazilat Ishkanian, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: August 24, 2007
• First Posted: August 27, 2007
• Study Start: June 1, 2007
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: November 25, 2014

Record last verified: 2014-11

Locations

US (1)