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


Phase 1
18 Years
N/A
Not Enrolling
Both
Malignant Glioma, Glioblastoma, Gliosarcoma

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Trial Information

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


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.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Authority:

United States: Food and Drug Administration

Study ID:

AP23573-04-103

NCT ID:

NCT00087451

Start Date:

July 2004

Completion Date:

November 2005

Related Keywords:

  • Malignant Glioma
  • Glioblastoma
  • Gliosarcoma
  • Progressive or recurrent malignant glioma
  • Glioblastoma
  • Glioma
  • Gliosarcoma

Name

Location

M.D. Anderson Cancer CenterHouston, Texas  77030
Center For Neuro-Oncology, Dana Farber Cancer InstituteBoston, Massachusetts  02115
The Brain Tumor Center at Duke, Duke University Medical CenterDurham, North Carolina  27710
Brain Tumor Institute, The Cleveland ClinicCleveland, Ohio  44195