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Ifosfamide With or Without O(6)-Benzylguanine in Treating Patients With Unresectable, Metastatic Solid Tumors
This study has been completed.

First Received on July 8, 2004.   Last Updated on February 6, 2009   History of Changes
Sponsor: University of Chicago
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00086970
  Purpose

RATIONALE: Drugs used in chemotherapy, such as ifosfamide and O(6)-benzylguanine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining ifosfamide with O(6)-benzylguanine may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of O(6)-benzylguanine when given together with ifosfamide and to see how well it works compared to ifosfamide alone in treating patients with unresectable metastatic solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
 Biological: filgrastim
Drug: O6-benzylguanine
Drug: ifosfamide
 Phase I

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study Of BG In Combination With Ifosfamide For Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer
Drug Information available for: O(6)-Benzylguanine Filgrastim Lenograstim Granulocyte colony-stimulating factor Ifosfamide
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: August 2004
Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of O6-benzylguanine when administered with standard high-dose ifosfamide in patients with unresectable, metastatic solid tumors.
  • Determine whether O6-benzylguanine enhances ifosfamide-mediated myelosuppression in patients treated with this regimen.
  • Determine the relationship between O6-benzylguanine dose and intra-individual variability in the degree of myelosuppression in patients treated with this regimen.
  • Determine the safety and toxicity of this regimen in these patients.

Secondary

  • Determine the effect of O6-benzylguanine on pharmacodynamic endpoints, including apoptosis and DNA damage, in patients treated with this regimen.
  • Determine the pharmacokinetics of O6-benzylguanine and its major metabolite, 8-oxoBG, in patients treated with this regimen.

OUTLINE: This is a randomized, open-label, multicenter, dose-escalation study of O6-benzylguanine.

  • Course 1: All patients receive high-dose ifosfamide IV continuously over 72 hours on days 1-3.

  • Course 2: Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive high-dose ifosfamide as in course 1.
    • Arm II: Patients receive a bolus dose of O6-benzylguanine (BG) IV over 1 hour on day 1 followed by BG IV continuously and high-dose ifosfamide IV continuously over 72 hours on days 1-3.

Cohorts of 6-12 patients receive escalating doses of BG (administered as a bolus and as a continuous infusion during course 2) until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 or 4 of 12 patients experience dose-limiting toxicity.

  • Course 3 and all subsequent courses: All patients receive BG (at the MTD determined in course 2, arm II) and high-dose ifosfamide as in course 2, arm II.

In all courses, all patients also receive filgrastim (G-CSF) beginning on day 5 and continuing until blood counts recover.

In all courses and in both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A minimum of 32 patients (at least 2 in arm I and at least 24 in arm II) will be accrued for this study within 12-15 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor

    • Unresectable, metastatic disease
    • No primary tumors
  • Eligible for high-dose ifosfamide-based therapy
  • No known brain metastases

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1 OR
  • Karnofsky 70-100%

Life expectancy

  • More than 12 weeks

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • AST and ALT ≤ 2.5 times upper limit of normal
  • Bilirubin normal

Renal

  • Creatinine normal OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 weeks after study participation
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to O6-benzylguanine or other study agents
  • No concurrent uncontrolled illness
  • No active or ongoing infection
  • No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 24 hours since prior colony-stimulating factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
  • No prior hematopoietic stem cell transplantation
  • No concurrent pegfilgrastim
  • No concurrent immunotherapy

Chemotherapy

  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent hormonal therapy

Radiotherapy

  • More than 4 weeks since prior radiotherapy and recovered
  • No concurrent therapeutic radiotherapy

Surgery

  • Not specified

Other

  • More than 4 weeks since prior anticancer therapy
  • No more than 2 prior cytotoxic regimens
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies
  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00086970

Locations
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
Sponsors and Collaborators
University of Chicago
National Cancer Institute (NCI)
Investigators
Study Chair: Sonali M. Smith, MD University of Chicago
  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

ClinicalTrials.gov Identifier: NCT00086970     History of Changes
Other Study ID Numbers: CDR0000371909, UCCRC-12999B, NCI-6461
Study First Received: July 8, 2004
Last Updated: February 6, 2009
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Ifosfamide
Isophosphamide mustard
O(6)-benzylguanine
Lenograstim
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012



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