Safety Study of AP23573 in Patients With Progressive or Recurrent Glioma (8669-023)(COMPLETED)

August 18, 2015 updated by: Merck Sharp & Dohme LLC

A Phase I Sequential Ascending Dose Trial of AP23573 in Patients With Progressive or Recurrent Malignant Glioma

A Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The primary objective of the study is to determine the safety, tolerability, and maximum tolerated dose (MTD) of AP23573 when administered intravenously once daily for five days repeated every two weeks to patients with progressive or recurrent gliomas who have failed standard therapy and who are or are not receiving enzyme-inducing anticonvulsant (EIAC) medications.

The secondary objectives are to: characterize the pharmacokinetic profile of AP23573 when administered daily for five days repeated every two weeks at the indicated dosage levels in patients receiving and not receiving EIAC; describe the progression-free survival at six months; describe changes in proteins affected by mTOR inhibition; describe single timepoint status of proteins affected by mTOR inhibition in tumor tissue surgical specimens after AP23573 dosing; describe the status of key proteins in the mTOR signaling pathway in archival tumor samples, if available; describe health-related quality of life at the start of the trial and prior to study drug infusion and at various timepoints throughout the trial.

Protocol Outline:

This is a Phase I, open-label, non-randomized, sequential dose escalation cohort trial of the safety, tolerability, and MTD of AP23573 when administered intravenously as a 30-minute infusion, once daily for five days, repeated every two weeks, to patients with progressive or recurrent malignant glioma.

Study Type

Interventional

Enrollment (Actual)

11

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Center For Neuro-Oncology, Dana Farber Cancer Institute
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • The Brain Tumor Center at Duke, Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Brain Tumor Institute, The Cleveland Clinic
    • Texas
      • Houston, Texas, United States, 77030
        • M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria (Patients must meet each of the following criteria to be eligible for participation in the trial):

  • Male or female patients ≥ 18 years of age
  • Patients must have a radiographically suspected progressive or recurrent primary malignant glioma (glioblastoma multiforme or gliosarcoma) and must have failed standard therapy. Patients may not have received any systemic therapy for the treatment of this recurrence or relapse
  • Patients must be candidates for surgical resection or open biopsy of the tumor
  • Patients who have had previous surgical resection(s) are eligible
  • Patients must have had minimum prior therapy of radiotherapy and documented progression of disease thereafter
  • Patients must have had a tissue proven malignant glioma
  • A minimum interval of at least four weeks prior to the first dose of AP23573 must have elapsed for all patients enrolling after either prior surgery or completion of prior external beam radiotherapy for initial primary diagnosis
  • A minimum interval of four weeks prior to the first dose of AP23573 must have elapsed since receipt of any investigational therapy or any other chemotherapy
  • Patients in the EIAC cohorts must be presently receiving a stable dose of EIAC (e.g., dilantin, phenytoin, etc.) for at least two weeks prior to the first dose of AP23573
  • For patients on corticosteroids, the dose must be stable for at least one week prior to the first dose of AP23573
  • Patients must be neurologically stable for at least two weeks prior to the first dose of AP23573
  • Patients must have an ECOG performance status of 0 or 1
  • Patients must either not be of childbearing potential or have agreed to use a medically effective method of contraception
  • Patients must have adequate hematologic, renal and liver function as specified in the protocol
  • Patients must be able to understand and give written informed consent

Exclusion Criteria (Patients meeting any of the following criteria are ineligible for participation in the trial):

  • Women who are pregnant or lactating
  • Patients with known or suspected hypersensitivity to either drugs formulated with polysorbate 80 (Tween) or any other excipient contained in the study drug formulation
  • Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin)
  • Patients with significant cardiovascular disease, as specified in the protocol
  • Patients with known HIV infection
  • Patients with any active infection requiring prescribed intervention
  • Patients receiving immunosuppressive agents other than prescribed corticosteroids
  • Patients who have had prior therapy with rapamycin, any rapamycin analog or tacrolimus
  • Patients with inadequate recovery from any prior surgical procedure or patients having undergone any major surgical procedure within two weeks prior to the first dose of AP23573
  • Patients with any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the study drug
  • Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies
  • Patients with another primary malignancy within the past three years (except for non-melanoma skin cancers and cervical carcinomas in situ)
  • Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements
  • Patients are not permitted any chemotherapeutic agents or other antineoplastic agents either during or within four weeks prior to the first dose of AP23573. Additional excluded drugs and treatments are specified in the protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Ariad Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Actual)

November 1, 2005

Study Completion (Actual)

November 1, 2005

Study Registration Dates

First Submitted

July 8, 2004

First Submitted That Met QC Criteria

July 12, 2004

First Posted (Estimate)

July 13, 2004

Study Record Updates

Last Update Posted (Estimate)

August 19, 2015

Last Update Submitted That Met QC Criteria

August 18, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8669-023
  • AP23573-04-103

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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