Clinical Trial: Erlotinib and Temsirolimus in Treating Patients With Recurrent Malignant Glioma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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

Detailed Summary:

PRIMARY OBJECTIVES:

I. To define the maximum tolerated dose (MTD) of OSI-774 (erlotinib; Tarceva) in combination with CCI-779 (temsirolimus) in patients with recurrent malignant glioma who are not taking enzyme-inducing anti-epileptic drugs (EIAEDs). (Phase I) II. To characterize the safety profile of OSI-774 (erlotinib) and CCI-779 (temsirolimus). (Phase I) III. To characterize the pharmacokinetics of OSI-774 (erlotinib) and CCI-779 (temsirolimus). (Phase I) IV. To determine the efficacy of OSI-774 (erlotinib) and CCI-779 (temsirolimus) in patients with recurrent malignant glioma as measured by 6-month progression-free survival. (Phase II)

SECONDARY OBJECTIVES:

I. Overall progression-free survival. (Phase II) II. Response. (Phase II)

TERTIARY OBJECTIVES:

I. To explore the association of response to treatment to the molecular phenotype of the tumor. (Phase II) II. Determine whether OSI-774 (erlotinib) and CCI-779 (temsirolimus) inhibits EGFR and mTOR and the PI3K-AKT-mTOR and RAS-ERK signaling pathways in tumor specimens taken from malignant glioma patients undergoing surgery. (Phase II) III. Tumor concentration of OSI-774 (erlotinib) and CCI-779 (temsirolimus). (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 o
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximum Tolerated Dose (Phase I) [ Time Frame: based on first 4 weeks of treatment - cycle 1 ]

    Oral erlotinab at 150mg constant dose, 3 pts will be treated with temsirolimus IV with escalating doses, starting at 50mg. Doses will increase or decrease based on toxicity observed.

    3 pts will be treated at each dose level - 3 dose levels were observed: 50mg, 25mg, and 15mg

  • Safety/Dose Limiting Toxities Phase I [ Time Frame: first 4 weeks of treatment ]

    Dose limiting toxities defined as: grade 3 thrombocytopenia, grade 4 anemia and neutropenia, grade >/= nonhematologic toxicity, and failure to recover from toxicites to be eligible for retreatment in 2 weeks of the last dose of either drug. Also grade 3 nonhematologic toxicities only if they wre refractory to maxiaml medical therapy.

    MTD defined as dose at which fewer than one-third of patients experienced a DLT

    Outcome measure defines number of participants who had a defined dose limiting toxicity.

  • Efficacy - Response Phase 1 [ Time Frame: at least 8 weeks of treatment ]

    pt must have at least 8 weeks of treatment to receive MRI scan, scans are every other cycle (every 2 months). Response measured by a bidimensionally measured leison and clearly defined margins by CT or MRI scan.

    Complete Response (CR): complete disappearance of all measurab

    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: June 2, 2005
    Date Started: April 2005
    Date Completion:
    Last Updated: May 29, 2015
    Last Verified: May 2015