Evaluation of a Promising New Combination of Protein Kinase Inhibitors on Organotypic Cultures of Human Renal Tumors
NCT ID: NCT03571438
Last Updated: 2020-01-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
NA
100 participants
INTERVENTIONAL
2017-10-16
2024-09-30
Brief Summary
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The population targeted by the combination for use in clinical practice is patients with metastatic clear cell renal cell carcinoma.
Current treatments for these patients are Sunitinib, Pazopanib and Temsirolimus.
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Detailed Description
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Thus, in 2005, the first targeted therapies in kidney cancer came with protein kinase inhibitors including mTOR (mammilian target of rapamycin) inhibitors (Temsirolimus and Everolimus) and VEGFR inhibitors (Sunitinib, Sorafenib, Pazopanib and Axitinib).
Nevertheless resistance to these treatments appeared with their prolonged use as monotherapy in all cases. One of the main mechanisms of this therapeutic escape is the adaptation of the tumor cell via the use of an alternative pathway of deregulation of cell signaling.
Thus emerged the idea of simultaneously treating multiple targets to prevent the tumor cell from adapting. Phase I / II therapeutic trials have already been initiated with the combination of anti-BRAF (proto-oncogene B-Raf) and anti-MEK (MAP-ERK kinase) in metastatic melanoma or with the combination of anti-EGFR (epidermal growth factor receptor) and anti-MET in lung and breast cancer. The results are very promising since we observe a synergistic effect of two targeted therapies combined.
In kidney cancer, this escape phenomenon is also observed (example of the mTORC2 (mammilian target of rapamycin complex 2) crosstalk on AKT which limits the effect of mTORC1 (mammilian target of rapamycin complex 1) inhibitors at the level of the PI3 kinase signaling pathway).
It is therefore time to check if this strategy is applicable in kidney cancer. The investigators have, through a chemo-genomic screening of a hundred molecules stored in the CEA (French Alternative Energies and Atomic Energy Commission) chemical bank, found a combination of inhibitors targeting the kinases CK2 and ATM very effective on a human cell line of renal cell carcinoma clear. This combination has been tested on conventional cultures as well as on more innovative 3D cultures, better reproducing the tumor environment. The preliminary results obtained show that the combination is clearly more efficient in a 3D model as well as on the VHL-line (von Hippel-Lindau) in hypoxic condition, which is very encouraging.
In the context of preclinical validation, it is now essential to evaluate the therapeutic potential of these molecules by comparing their efficiency with those currently selected.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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CK2(CX4945) and ATM(Ku 60019)
Treatment of cell culture with a combination of CK2 and ATM inhibitors serine/ threonin Kinase combination
CK2 and ATM inhibitors serine/ threonin Kinase combination
Treatment of cell culture with CK2 and ATM inhibitors serine/ threonin Kinase combination
Sunitinib
Treatment of cell culture with Sunitinib
Sunitinib
Treatment of cell culture with Sunitinib
Pazopanib
Treatment of cell culture with Pazopanib
Pazopanib
Treatment of cell culture with Pazopanib
Temsirolimus
Treatment of cell culture with Temsirolimus
Temsirolimus
Treatment of cell culture with Temsirolimus
Interventions
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CK2 and ATM inhibitors serine/ threonin Kinase combination
Treatment of cell culture with CK2 and ATM inhibitors serine/ threonin Kinase combination
Sunitinib
Treatment of cell culture with Sunitinib
Pazopanib
Treatment of cell culture with Pazopanib
Temsirolimus
Treatment of cell culture with Temsirolimus
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* Absence or withdrawal of the informed consent of the patient.
* Tumors smaller than 2 cm on preoperative imaging
18 Years
ALL
No
Sponsors
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University Hospital, Grenoble
OTHER
Responsible Party
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Locations
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Grenoble Alps Hospital
Grenoble, , France
Countries
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Central Contacts
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Facility Contacts
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Jean-Luc Descotes, PU-PH
Role: primary
Other Identifiers
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38RC17.063
Identifier Type: -
Identifier Source: org_study_id
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