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A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors


Phase 1
N/A
21 Years
Not Enrolling
Both
Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

A Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Victor Aquino, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Simmons Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01837

NCT ID:

NCT00003288

Start Date:

August 1998

Completion Date:

Related Keywords:

  • Unspecified Childhood Solid Tumor, Protocol Specific
  • unspecified childhood solid tumor, protocol specific
  • Neoplasms

Name

Location

Baylor College of MedicineHouston, Texas  77030
Roswell Park Cancer InstituteBuffalo, New York  14263
University of Alabama Comprehensive Cancer CenterBirmingham, Alabama  35294
Emory University Hospital - AtlantaAtlanta, Georgia  30322
Johns Hopkins Oncology CenterBaltimore, Maryland  21287
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Simmons Cancer Center - DallasDallas, Texas  75235-9154
Sylvester Cancer Center, University of MiamiMiami, Florida  33136
Children's Hospital of MichiganDetroit, Michigan  48201
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
University of California San Diego Cancer CenterLa Jolla, California  92093-0658
State University of New York - Upstate Medical UniversitySyracuse, New York  13210
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
University of Kansas Medical CenterKansas City, Kansas  66160-7353
Hackensack University Medical CenterHackensack, New Jersey  07601
Floating Hospital for ChildrenBoston, Massachusetts  02111
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Lucile Packard Children's Hospital at StanfordPalo Alto, California  94304
Saint Jude Children's Research HospitalMemphis, Tennessee  38105-2794
Children's Memorial Hospital, ChicagoChicago, Illinois  60614