Tirapazamine Plus Cyclophosphamide in Treating Children With Refractory Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003288
First received: November 1, 1999
Last updated: February 4, 2013
Last verified: April 2000
  Purpose

Phase I trial to study the effectiveness of tirapazamine plus cyclophosphamide in treating children who have refractory solid tumors. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.


Condition Intervention Phase
Unspecified Childhood Solid Tumor, Protocol Specific
Biological: filgrastim
Drug: cyclophosphamide
Drug: tirapazamine
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors

Resource links provided by NLM:


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

Enrollment: 12
Study Start Date: August 1998
Primary Completion Date: June 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
See arm description.
Biological: filgrastim Drug: cyclophosphamide Drug: tirapazamine

Detailed Description:

OBJECTIVES:

I. Determine the maximum tolerated dose and the dose limiting toxicity of tirapazamine when administered with cyclophosphamide as intravenous infusions to children with refractory solid tumors.

II. Determine the incidence and severity of other toxicities of tirapazamine and cyclophosphamide in these patients.

III. Determine a safe and tolerable dose of tirapazamine administered with cyclophosphamide for a phase II study for the same indications.

IV. Determine the pharmacokinetics of tirapazamine in children and adolescents receiving the combination of tirapazamine and cyclophosphamide.

V. Determine the preliminary evidence of antitumor activity of tirapazamine and cyclophosphamide.

OUTLINE: This is a dose escalation study.

Patients receive tirapazamine by 2 hour intravenous infusion (hours 0-2) followed 2 hours later by a 30 minute intravenous infusion of cyclophosphamide. This course is repeated every 3 weeks in patients with partial/complete response or stable disease for a maximum of 1 year. Cohorts of 3-6 patients each are treated at each dose level of tirapazamine. Dose escalation of tirapazamine occurs when 0 of 3 patients or 1 of 6 patients has experienced dose limiting toxicity (DLT). If DLT is experienced in 1 of 3 patients at a given dose level, up to 3 additional patients are treated at that same dose level. If none of the 3 additional patients at that dose level experiences DLT, the dose is escalated. If DLT is experienced in 1 or more of the additional 3 patients, the maximum tolerated dose (MTD) has been exceeded and 3 patients are treated at the next lower dose level (defined as the MTD). A total of six patients are treated at the MTD. If DLT is proved to be neutropenia, patients must then also meet the additional eligibility criteria listed for stratum 2. If neutropenia continues to be the DLT in stratum 2, then additional patients receive subcutaneous filgrastim (granulocyte colony-stimulating factor; G-CSF) beginning 24 hours after cyclophosphamide. A second MTD may be determined for chemotherapy with G-CSF. Patients are followed every 6 months for 4 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor that is refractory to conventional therapy or for which no effective therapy is known
  • Brain tumors eligible Brainstem gliomas may waive histological verification requirement
  • Neurologic deficits associated with CNS malignancies must be stable for a minimum of 4 weeks prior to study
  • No leukemia Stratum 2
  • No marrow involvement

PATIENT CHARACTERISTICS:

  • Age: 21 and under
  • Performance status: Karnofsky or Lansky 50-100%
  • Life expectancy: At least 8 weeks
  • Absolute neutrophil count at least 1,000/mm3
  • Platelet count at least 75,000/mm3
  • Hemoglobin at least 9 g/dL
  • Bilirubin less than 1.5 mg/dL
  • SGPT less than 5 times normal
  • Creatinine normal for age OR creatinine clearance at least 70 mL/min
  • Shortening fraction at least 27% of normal OR ejection fraction greater than 50% of normal
  • Not pregnant or nursing
  • Negative pregnancy test required

PRIOR CONCURRENT THERAPY:

  • No concurrent anticancer therapy
  • At least 6 months since bone marrow transplant and no evidence of graft versus host disease
  • At least 1 week since growth factors
  • No concurrent granulocyte colony-stimulating factor
  • Recovered from prior immunotherapy
  • Stratum 2: No prior bone marrow transplantation (with or without total body irradiation)
  • At least 6 weeks since prior nitrosourea
  • At least 2 weeks since other prior myelosuppressive chemotherapy
  • Dexamethasone must be a stable or decreasing dose for 2 weeks prior to study
  • Recovered from prior chemotherapy
  • Stratum 2: No more than 2 prior chemotherapy regimens
  • At least 2 weeks since local palliative radiotherapy (small port)
  • At least 6 months since prior substantial bone marrow radiation (e.g., cross- sectional radiotherapy [greater than 24 Gy], total body irradiation, hemi- pelvic radiotherapy)
  • Recovered from prior radiotherapy
  • Stratum 2: No prior central axis radiation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003288

  Show 28 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Victor Aquino, MD Simmons Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003288     History of Changes
Other Study ID Numbers: NCI-2012-01837, POG-9675, CDR0000066219
Study First Received: November 1, 1999
Last Updated: February 4, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Neoplasms
Cyclophosphamide
Tirapazamine
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014