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
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: erlotinib hydrochloride
Drug: temsirolimus
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of OSI-774 (Erlotinib) and CCI-779 (Temsirolimus) in Patients With Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • Response rate (Phase II) [ Designated as safety issue: No ]

Enrollment: 68
Study Start Date: April 2005
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112736

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Pennsylvania
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-6220
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Patrick Y. Wen, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
Publications:
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.

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00112736     History of Changes
Obsolete Identifiers: NCT00267878
Other Study ID Numbers: ABTC-0402 CDR0000429553, U01CA062399, ABTC-0402, NCI-06-C-0053
Study First Received: June 2, 2005
Last Updated: November 29, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
recurrent adult brain tumor
adult anaplastic astrocytoma
adult anaplastic oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
adult glioblastoma
adult mixed glioma

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Sirolimus
Everolimus
Erlotinib
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 15, 2014