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CompletedNCT00087451Updated Aug 19, 2015

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

A Phase 1 interventional study of AP23573 in Malignant Glioma, Glioblastoma and Gliosarcoma, sponsored by Merck Sharp & Dohme LLC. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-08-19.

Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
11
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Malignant Glioma
  • Glioblastoma
  • Gliosarcoma

Keywords

  • Progressive or recurrent malignant glioma
03

In context

Glioma

1,425 studies on the registry are indexed under Glioma; 355 are open to participants now.

This study's enrollment of 11 is below the median of 32 across 1,085 interventional studies indexed under Glioma.

Browse Glioma studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,159 studies on the registry; 133 are open to participants now.

Of its 497 completed or terminated interventional studies of FDA-regulated products, 369 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
11 participants (actual)

Interventions

  • ridaforolimus

    Also known as: deforolimus, MK-8669, ridaforolimus was also known as deforolimus until May 2009

06

Study locations

4 sites
  • Center For Neuro-Oncology, Dana Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • The Brain Tumor Center at Duke, Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Brain Tumor Institute, The Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • M.D. Anderson Cancer Center
    Houston, Texas 77030, United States
07

References and documents

Publications

  • Reardon DA, Wen PY, Alfred Yung WK, Berk L, Narasimhan N, Turner CD, Clackson T, Rivera VM, Vogelbaum MA. Ridaforolimus for patients with progressive or recurrent malignant glioma: a perisurgical, sequential, ascending-dose trial. Cancer Chemother Pharmacol. 2012 Apr;69(4):849-60. doi: 10.1007/s00280-011-1773-y. Epub 2011 Oct 30. PubMed 22037923 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 19, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00087451
Responsible party
Sponsor
First posted
Jul 13, 2004
Start date
Jul 2004
Primary completion
Nov 2005
Completion
Nov 2005
Last update
Aug 19, 2015
View the source record on ClinicalTrials.gov ↗

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