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

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

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Trial Information

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


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

- 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

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


- 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

- 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



- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 8 weeks


- 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)


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

- SGOT less than 1.5 times ULN


- Creatinine less than 1.5 mg/dL


- Cholesterol less than 350 mg/dL

- Triglycerides less than 400 mg/dL

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

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

- 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


Biologic therapy

- At least 1 week since prior interferon


- 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


- See Disease Characteristics

- At least 4 weeks since prior radiotherapy


- See Disease Characteristics


- Recovered from prior therapy

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

Type of Study:


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:


Principal Investigator

Timothy F. Cloughesy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




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



Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781