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A Phase I/II Trial of SU5416 in Patients With Recurrent High Grade Astrocytomas or Mixed Gliomas


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Brain and Central Nervous System Tumors

Thank you

Trial Information

A Phase I/II Trial of SU5416 in Patients With Recurrent High Grade Astrocytomas or Mixed Gliomas


OBJECTIVES: Phase I:

- Determine the maximum tolerated dose of SU5416 in patients with recurrent malignant
glioma who are, as well as those who are not, taking enzyme-inducing antiepileptic
drugs.

- Determine the toxic effects (safety profile) of this drug in this patient population.

- Characterize the pharmacokinetics of this drug in these patients.

- Develop exploratory data relative to surrogate endpoints of angiogenic activity in
vivo, including functional imaging and in vitro assays of endothelial cell inhibition
and serum angiogenic peptides.

Phase II:

- Determine the efficacy of SU5416, in terms of 6-month progression-free survival, in
patients with recurrent high-grade glioma.

- Determine, further, the safety profile of the phase II dose of this drug in this
patient population.

- Develop exploratory data relative to surrogate endpoints of angiogenic activity in vivo
including functional imaging and in vitro assays of endothelial cell inhibition and
serum angiogenic peptides.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
concurrent enzyme-inducing antiepileptic drugs (no vs yes).

Patients receive SU5416 IV on days 1 and 4 weekly for 4 weeks. Courses repeat every 4 weeks
in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of SU5416 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. Once the MTD has been determined, additional
patients are accrued to the phase II portion of the study. These patients receive SU5416 IV,
as in the phase I portion, at the appropriate MTD established in phase I.

Patients are followed for survival.

PROJECTED ACCRUAL: At least 30 patients will be accrued for the phase I dose-escalation
portion of this study within 10 months. An additional 48 patients (32 with glioblastoma
multiforme and 16 with anaplastic glioma) will be accrued for the phase II portion of this
study within 6-8 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically proven supratentorial malignant primary glioma, including:

- Glioblastoma multiforme

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed oligoastrocytoma

- Malignant astrocytoma not otherwise specified

- Benign or malignant meningiomas, including brain and spinal meningiomas

- Patients with meningiomas are excluded from phase II portion of study

- Must have shown unequivocal evidence of tumor recurrence or progression by CT scan or
MRI

- Must have failed prior radiotherapy

- Must have prestudy contrast MRI or contrast CT scan of brain on stable steroid dose
within the past 14 days

- Must be on stable (unchanged) dose of steroids for at least 5 days before scans

- Phase II:

- Must have completed radiotherapy at least 2 months prior to enrollment

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- Karnofsky 60-100%

Life expectancy:

- More than 8 weeks

Hematopoietic:

- WBC at least 2,300/mm^3

- Platelet count at least 100,000/mm^3

- Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic:

- SGOT less than 2.5 times upper limit of normal

- Bilirubin normal

- No significant active hepatic disease

Renal:

- Creatinine less than 1.5 mg/dL OR

- Creatinine clearance at least 60 mL/min

- No significant active renal disease

Cardiovascular:

- No uncompensated coronary artery disease on ECG or physical examination

- No history of myocardial infarction or severe/unstable angina within the past 6
months

- No deep venous or arterial thrombosis within the past 3 months

Pulmonary:

- No pulmonary embolism within the past 3 months

Other:

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 2 months after study

- No other serious concurrent illness

- No significant active psychiatric disease

- No diabetes mellitus with severe peripheral vascular disease

- No other malignancy within the past 3 years except nonmelanoma skin cancer or
carcinoma in situ of the cervix

- No serious active infection

- No other concurrent disease that would obscure toxic effects or dangerously alter
drug metabolism

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 3 weeks since prior biologic therapy (e.g., interferon) and recovered

- No concurrent immunotherapy

Chemotherapy:

- Phase I:

- No more than 2 prior chemotherapy regimens for recurrent disease

- Phase II:

- No more than 1 prior chemotherapy regimen for recurrent disease

- At least 2 weeks since prior vincristine

- At least 6 weeks since prior nitrosoureas

- At least 3 weeks since prior procarbazine

- Recovered from prior chemotherapy

- No concurrent chemotherapy

Endocrine therapy:

- See Disease Characteristics

- At least 3 weeks since prior endocrine therapy (e.g., tamoxifen) and recovered

Radiotherapy:

- See Disease Characteristics

- No concurrent radiotherapy

Surgery:

- Recovered from prior surgery

- Recent prior resection of recurrent or progressive tumor allowed

Other:

- No other concurrent investigational agents

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Howard A. Fine, MD

Investigator Role:

Study Chair

Investigator Affiliation:

NCI - Neuro-Oncology Branch

Authority:

United States: Federal Government

Study ID:

CDR0000067527

NCT ID:

NCT00004868

Start Date:

February 2000

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent adult brain tumor
  • adult meningioma
  • adult glioblastoma
  • adult anaplastic astrocytoma
  • adult anaplastic oligodendroglioma
  • adult mixed glioma
  • adult grade III meningioma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Astrocytoma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Texas - MD Anderson Cancer CenterHouston, Texas  77030-4009
University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Jonsson Comprehensive Cancer Center, UCLALos Angeles, California  90095-1781
Simmons Cancer Center - DallasDallas, Texas  75235-9154
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
University of Pittsburgh Cancer InstitutePittsburgh, Pennsylvania  15213
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Children's Hospital of PittsburghPittsburgh, Pennsylvania  15213
Neuro-Oncology BranchBethesda, Maryland  20892