NCT00613132

Phase I Dose Escalation of Gleevec in Combination With RAD001 Plus Hydroxyurea for Patients With Recurrent Malignant Glioma

Completed Phase 1 Last updated 19 February 2013

What this trial tests

Phase 1 trial testing Gleevec, RAD001, and Hydroxyurea in Glioblastoma in 78 participants. Completed in 1 January 2013.

Timeline

1 May 2005

Primary endpoint
1 August 2008

1 January 2013

Quick facts

Lead sponsor	Annick Desjardins
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	78
Start date	1 May 2005
Primary completion	1 August 2008
Estimated completion	1 January 2013
Sites	1 location across United States

Drugs / interventions tested

• Gleevec, RAD001, and Hydroxyurea — full drug profile →

Conditions studied

• Glioblastoma — all drugs for Glioblastoma →
• Gliosarcoma — all drugs for Gliosarcoma →

Sponsor

Annick Desjardins — full company profile →

Who can join

18 and older, any sex, with Glioblastoma or Gliosarcoma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• To determine MTD & DLT & Imatinib mesylate & RAD001 when combined w Hydroxyurea among pt w GBM
  Time frame: 6 months

Sponsor's own description

Primary objective To determine maximum tolerated dose \& dose limiting toxicity of imatinib mesylate \& RAD001 when combined w fixed doses of hydroxyurea among pts w recurrent GBM who are on \& not on enzyme-inducing anti-convulsants including pts not on anti-epileptic drugs Secondary objective To assess safety \& tolerability of imatinib mesylate in combo w RAD001 \& hydroxyurea in this population To characterize single-dose \& repeated-dose pharmacokinetic profiles of imatinib mesylate \& RAD001 combo therapy in this pt population.

To assess antiangiogenic effects, pre- and post-treatment, of imatinib mesylate, RAD001 \& hydroxyurea combo therapy, using DCE-MRI to evaluate changes in extent of vascular permeability, perfusion \& relative tumor blood volume; to explore assessment of tumor cellularity \& tumor cell death by changes in DWI-MRI as quantitated by apparent diffusion coefficient maps.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. PI3K/Akt/mTOR signaling pathway and targeted therapy for glioblastoma.
   Li X, Wu C, Chen N, Gu H, et al · · 2016 · cited 406× · PMID 26967052 · DOI 10.18632/oncotarget.7961
2. Pathway inhibition: emerging molecular targets for treating glioblastoma.
   Wick W, Weller M, Weiler M, Batchelor T, et al · · 2011 · cited 103× · PMID 21636705 · DOI 10.1093/neuonc/nor039
3. Combined inhibition of AKT/mTOR and MDM2 enhances Glioblastoma Multiforme cell apoptosis and differentiation of cancer stem cells.
   Daniele S, Costa B, Zappelli E, Da Pozzo E, et al · · 2015 · cited 68× · PMID 25898313 · DOI 10.1038/srep09956
4. Experimental approaches for the treatment of malignant gliomas.
   Arko L, Katsyv I, Park GE, Luan WP, et al · · 2010 · cited 65× · PMID 20546782 · DOI 10.1016/j.pharmthera.2010.04.015
5. Unique biology of gliomas: challenges and opportunities.
   Watkins S, Sontheimer H. · · 2012 · cited 53× · PMID 22683220 · DOI 10.1016/j.tins.2012.05.001
6. The Molecular and Microenvironmental Landscape of Glioblastomas: Implications for the Novel Treatment Choices.
   Di Cintio F, Dal Bo M, Baboci L, De Mattia E, et al · · 2020 · cited 28× · PMID 33324155 · DOI 10.3389/fnins.2020.603647
7. Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies.
   Thaker NG, Pollack IF. · · 2009 · cited 24× · PMID 19951140 · DOI 10.1586/ern.09.116
8. Immunohistochemical Assessment of Phosphorylated mTORC1-Pathway Proteins in Human Brain Tumors.
   Harter PN, Jennewein L, Baumgarten P, Ilina E, et al · · 2015 · cited 18× · PMID 25993328 · DOI 10.1371/journal.pone.0127123