Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00112736
First received: June 2, 2005
Last updated: November 29, 2012
Last verified: November 2012

June 2, 2005
November 29, 2012
April 2005
April 2010   (final data collection date for primary outcome measure)
  • Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
  • Safety (Phase I) [ Designated as safety issue: Yes ]
  • Pharmacokinetics (Phase I) [ Designated as safety issue: No ]
  • Efficacy (Phase I) [ Designated as safety issue: No ]
  • Progression-free survival at 6 months (Phase II) [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00112736 on ClinicalTrials.gov Archive Site
Response rate (Phase II) [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma
Phase I/II Study of OSI-774 (Erlotinib) and CCI-779 (Temsirolimus) in Patients With Recurrent Malignant Glioma

RATIONALE: Erlotinib and temsirolimus and may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with erlotinib and to see how well they work in treating patients with recurrent malignant glioma.

OBJECTIVES:

Primary

  • 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)

Secondary

  • 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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
  • Drug: erlotinib hydrochloride
  • Drug: temsirolimus
Not Provided
  • Chang SM, Kuhn J, Lamborn K: Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas (MG) (NABTC 04-02). [Abstract] J Clin Oncol 27 (Suppl 15): A-2004, 2009.
  • Robins HI, Wen PY, Chang SM, et al.: Phase I study of erlotinib and CCI-779 (temsirolimus) for patients with recurrent malignant gliomas (MG) (NABTC 04-02). [Abstract] J Clin Oncol 25 (Suppl 18): A-2057, 2007.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
68
Not Provided
April 2010   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • 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 relapse
      • 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)

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Karnofsky 60-100%

Life expectancy

  • More than 8 weeks

Hematopoietic

  • WBC ≥ 2,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)

Hepatic

  • SGOT and SGPT ≤ 2.5 times upper limit of normal (ULN)
  • Total bilirubin normal

Renal

  • Creatinine < 1.5 mg/dL

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 1 week since prior interferon or thalidomide
  • No concurrent prophylactic filgrastim (G-CSF)
  • No concurrent anticancer immunotherapy

Chemotherapy

  • 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

Radiotherapy

  • 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 disease
  • No concurrent anticancer radiotherapy

Surgery

  • See Disease Characteristics
  • Prior resection of recurrent or progressive disease allowed provided patient has recovered

    • Residual disease after tumor resection is not required

Other

  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00112736
ABTC-0402 CDR0000429553, U01CA062399, ABTC-0402, NCI-06-C-0053
Not Provided
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Patrick Y. Wen, MD Dana-Farber Cancer Institute
Sidney Kimmel Comprehensive Cancer Center
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP