Coordinated Undermining of Survival Paths by 9 Repurposed Drugs (CUSP9v3)

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Coordinated Undermining of Survival Paths by 9 Repurposed Drugs Combined With Metronomic Temozolomide (CUSP9v3)

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria:

a) were pharmacologically well characterized,

b) had low likelihood of adding to patient side effect burden,

c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and

d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth.

We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol.

The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are: aprepitant, minocycline, disulfiram, celecoxib, sertraline, captopril, itraconazole, ritonavir, auranofin to be added to continuous low dose temozolomide.

We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma’s compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

DETAILS:

CLINICALTRIALS.GOV IDENTIFIER: NCT02770378

LOCATION: ULM, GERMANY

 

FUNDING SOUGHT: € 1.1m (PHASE 1 & 2)

FUNDING SECURED: COMPLETE

FUNDING PARTNERS:

acf

cwr

  • Please note that CUSP9V3 protocol had been modified to: aprepitant, minocycline, disulfiram, celecoxib, sertraline, captopril, itraconazole, ritonavir, auranofin. Clinicaltrials.gov identifier: NCT02770378

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If you are a physician who would be willing to prescribe this protocol to local patients, please register your interest using the form below. The authors of this study are available to be contacted when needed.

 

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Q: In this study design, does concern for the interests of the subject prevail over those of science and society?

Founding principal of the Declaration of Helsinki, subscribed to by the World Medical Association in 1975, as an extension of the Geneva Convention.

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