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Phase I/II Study of OSI-774 (Erlotinib) and CCI-779 (Temsirolimus) in Patients With Recurrent Malignant Glioma

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

Thank you

Trial Information

Phase I/II Study of OSI-774 (Erlotinib) and CCI-779 (Temsirolimus) in Patients With Recurrent Malignant Glioma



- Determine the maximum tolerated dose of temsirolimus when administered with erlotinib
in patients with recurrent malignant glioma. (Phase I)

- Determine the safety of this regimen in these patients. (Phase I)

- Determine the pharmacokinetics of this regimen in these patients. (Phase I)

- Determine the efficacy of this regimen, in terms of 6-month progression-free survival,
in these patients. (Phase II)


- Determine overall progression-free survival of patients treated with this regimen.
(Phase II)

- Determine response in patients treated with this regimen. (Phase II)

- Correlate response to treatment with the molecular phenotype of the tumor in these
patients. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of temsirolimus followed by a
phase II study. Patients are stratified according to study phase (I vs II), histology at
study enrollment (glioblastoma multiforme or gliosarcoma vs anaplastic glioma), preoperative
candidacy (yes vs no), and presence of measurable or evaluable disease (yes vs no).

- Phase I: Patients receive oral erlotinib once daily on days 1-28 and temsirolimus IV
over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence
of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of temsirolimus 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.

- Phase II: Patients receive temsirolimus at the MTD and erlotinib as in phase I.

- Phase II (preoperative component): Patients who are surgical candidates may opt to
undergo surgical resection of the tumor. Beginning 5-7 days before surgery, these
patients receive oral erlotinib once daily until surgery. Patients also receive
temsirolimus IV over 30 minutes at the MTD and then undergo surgical resection of the
tumor 3-24 hours later. Beginning 2-4 weeks after surgery, patients receive
temsirolimus at the MTD and erlotinib as in phase I.

PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for the phase I portion of the
study within 1-8 months. A total of 50 patients (32 patients with glioblastoma multiforme
and 18 with anaplastic glioma) will be accrued for the phase II portion of the study within
8-12 months.

Inclusion Criteria


- Histologically confirmed intracranial malignant glioma of 1 of the following types:

- Glioblastoma multiforme

- Gliosarcoma

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- Anaplastic mixed oligoastrocytoma

- Malignant astrocytoma not otherwise specified

- Prior low-grade glioma allowed provided a subsequent histological diagnosis of
high-grade malignant glioma has been made

- Unequivocal evidence of progressive disease by MRI or CT scan while on a stable dose
of steroids for ≥ 5 days

- Stable dose of steroids prior to MRI or CT scan is not required for patients
enrolled in the preoperative component of the phase II study

- Failed prior radiotherapy

- Meets 1 of the following criteria for treatment of prior relapses:

- Treatment for any number of prior relapses allowed (phase I patients only)

- Treated for no more than 2 prior relapses* (phase II patients only)

- Prior surgical resection for relapsed disease with no anticancer therapy
for up to 12 weeks followed by another surgical resection is considered 1

- Prior therapy for low-grade glioma followed by surgical diagnosis of
high-grade glioma is considered 1 relapse NOTE: *No more than 3 prior
therapies, including initial treatment and treatment for 2 relapses

- Unstained slides or paraffin tissue block available from ≥ 1 prior surgery (phase II)



- 18 and over

Performance status

- Karnofsky 60-100%

Life expectancy

- More than 8 weeks


- WBC ≥ 2,000/mm^3

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL (transfusion allowed)


- SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)

- Total bilirubin normal


- Creatinine < 1.5 mg/dL


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective barrier contraception during and for 3 months
after completion of study treatment

- Cholesterol ≤ 350 mg/dL

- Triglycerides ≤ 400 mg/dL

- No other malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix,
or cancer in complete remission that has not been treated within the past 3 years

- No active infection

- No serious medical illness

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

- No significant uncontrolled medical illness that would preclude study participation


Biologic therapy

- At least 1 week since prior interferon or thalidomide

- No concurrent prophylactic filgrastim (G-CSF)

- No concurrent anticancer immunotherapy


- At least 2 weeks since prior vincristine

- At least 6 weeks since prior nitrosoureas

- At least 3 weeks since prior procarbazine

- No prior temsirolimus

- No other concurrent anticancer chemotherapy

Endocrine therapy

- See Disease Characteristics

- At least 1 week since prior tamoxifen

- No concurrent anticancer hormonal therapy


- See Disease Characteristics

- At least 6 weeks since prior radiotherapy

- Prior interstitial brachytherapy or stereotactic radiosurgery allowed provided there
is evidence of true progressive disease (rather than radiation necrosis) by positron
emission tomography or thallium scan, MR spectroscopy, or surgical documentation of

- No concurrent anticancer radiotherapy


- See Disease Characteristics

- Prior resection of recurrent or progressive disease allowed provided patient has

- Residual disease after tumor resection is not required


- Recovered from all prior therapy

- At least 4 weeks since prior investigational agents

- At least 4 weeks since prior cytotoxic therapy

- At least 1 week since prior non-cytotoxic therapy (e.g., interferon, tamoxifen,
thalidomide, isotretinoin, etc.) except radiosensitizers

- At least 2 weeks since prior and no concurrent enzyme-inducing anti-epileptic drugs

- No prior erlotinib

- No other prior mTOR or epidermal growth factor receptor inhibitors

- No concurrent antiretroviral therapy for HIV-positive patients

- No other concurrent investigational drugs

- No other concurrent anticancer therapy

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (Phase I)

Safety Issue:


Principal Investigator

Patrick Y. Wen, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:

ABTC-0402 CDR0000429553



Start Date:

April 2005

Completion Date:

Related Keywords:

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



Memorial Sloan-Kettering Cancer Center New York, New York  10021
Duke Comprehensive Cancer Center Durham, North Carolina  27710
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute Boston, Massachusetts  02115
Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
UPMC Cancer Centers Pittsburgh, Pennsylvania  15232
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182