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A Modified Phase I/II Trial Of Rapamycin In Patients With Glioblastoma Multiforme


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

Thank you

Trial Information

A Modified Phase I/II Trial Of Rapamycin In Patients With Glioblastoma Multiforme


OBJECTIVES:

- Determine the maximum tolerated dose of sirolimus in patients with glioblastoma
multiforme.

- Determine the safety profile of this drug in these patients.

- Determine the efficacy of this drug, in terms of 6-month progression-free survival and
objective response, in these patients.

OUTLINE: This is a dose-escalation study.

- Phase I: Patients receive oral sirolimus for 5-7 days before surgery. Patients then
undergo surgical resection. Patients resume oral sirolimus once daily after full
recovery from surgery. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.

- Phase II: Patients receive oral sirolimus as in phase I at the dose determined in that
phase.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 3-12 patients will be accrued for phase I of the study within
3-12 months. A total of 32 patients will be accrued for phase II of the study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed intracranial glioblastoma multiforme

- Disease progression by MRI or CT scan

- Confirmation of true progressive disease (not radiation necrosis) by
positron-emission tomography, thallium scanning, MRI, or surgical documentation
required if patient received prior interstitial brachytherapy or stereotactic
radiosurgery

- Failed prior radiotherapy

- Phase I patients:

- Eligible for salvage surgery

- No limits on prior therapy

- Phase II patients:

- Tumor progression by MRI or CT scan required within the past 14 days if
recurrent disease is present

- No prior therapy for more than 3 relapses

- Recent resection of recurrent or progressive tumor allowed as long as all of the
following conditions apply:

- Recovered from surgery

- MRI or CT scan performed no more than 96 hours since prior surgery OR
within 4-6 weeks after surgery

- Baseline MRI or CT scan performed within 14 days of study entry

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 8 weeks

Hematopoietic

- WBC at least 3,000/mm^3

- Absolute neutrophil count at least 2,000/mm^3

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

- Hemoglobin at least 10 g/dL (transfusion allowed)

Hepatic

- Bilirubin less than 1.5 times upper limit of normal (ULN)

- SGOT less than 1.5 times ULN

Renal

- Creatinine less than 1.5 mg/dL

Other

- Cholesterol less than 350 mg/dL

- Triglycerides less than 400 mg/dL

- No concurrent disease that would obscure toxicity or dangerously alter drug
metabolism

- No other significant uncontrolled serious medical illness that would preclude study
participation

- No other cancer except non-melanoma skin cancer or carcinoma in situ of the cervix
unless patient is in complete remission and off all therapy for that disease for at
least 3 years

- No active infection

- No prior allergic reactions to compounds of similar chemical or biological
composition to sirolimus

- No psychiatric illness that would preclude study participation

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

- At least 1 week since prior interferon

Chemotherapy

- At least 2 weeks since prior vincristine

- At least 3 weeks since prior procarbazine

- At least 6 weeks since prior nitrosoureas

Endocrine therapy

- At least 1 week since prior tamoxifen

Radiotherapy

- See Disease Characteristics

- At least 4 weeks since prior radiotherapy

Surgery

- See Disease Characteristics

Other

- Recovered from prior therapy

- At least 1 week since prior noncytotoxic agents (except radiosensitizers)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (for phase 1)

Outcome Time Frame:

end of phase 1

Safety Issue:

Yes

Principal Investigator

Timothy F. Cloughesy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000257255

NCT ID:

NCT00047073

Start Date:

July 2002

Completion Date:

October 2007

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent adult brain tumor
  • adult glioblastoma
  • adult giant cell glioblastoma
  • adult gliosarcoma
  • Glioblastoma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms

Name

Location

Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781