Evaluation of a Promising New Combination of Protein Kinase Inhibitors on Organotypic Cultures of Human Renal Tumors (COMBOREIN)

January 16, 2020 updated by: University Hospital, Grenoble

The investigators objective is to test the combination directly on organotypic cultures of tumors from patients after their excision in the Department of Urology and Renal Transplantation of the University Hospital of Grenoble and to compare their efficacy with that of currently selected treatments in the clinic.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Given the failure of conventional therapies in kidney cancer, both chemo and radio resistant, it was necessary to seek therapeutic alternatives.

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.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Grenoble, France, 38043
        • Recruiting
        • Grenoble Alps Hospital
        • Contact:
          • Jean-Luc Descotes, PU-PH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • major patient treated at the University Hospital of Grenoble for a renal tumor with suspected or confirmed malignancy.This includes non-metastatic patients undergoing renal lumpectomy, partial nephrectomy or total nephrectomy, as well as metastatic or locally advanced cancer patients undergoing cytoreductive surgery who are eligible for medical treatment at the same time

Exclusion Criteria:

  • Contaminated patients with HIV and /or HBV (hepatitis B virus) and / or HCV (hepatitis C virus) positive serology.
  • Absence or withdrawal of the informed consent of the patient.
  • Tumors smaller than 2 cm on preoperative imaging

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: CK2(CX4945) and ATM(Ku 60019)
Treatment of cell culture with a combination of CK2 and ATM inhibitors serine/ threonin Kinase combination
Combination product: CK2 and ATM inhibitors serine/ threonin Kinase combination
Treatment of cell culture with CK2 and ATM inhibitors serine/ threonin Kinase combination
ACTIVE_COMPARATOR: Sunitinib
Treatment of cell culture with Sunitinib
Drug: Sunitinib
Treatment of cell culture with Sunitinib
ACTIVE_COMPARATOR: Pazopanib
Treatment of cell culture with Pazopanib
Drug: Pazopanib
Treatment of cell culture with Pazopanib
ACTIVE_COMPARATOR: Temsirolimus
Treatment of cell culture with Temsirolimus
Drug: Temsirolimus
Treatment of cell culture with Temsirolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of cell death on organotypic cultures of human renal tumors (Efficacy)
Time Frame: after the treatment period (between 48 and 96 hours)
Death cell rate on organotypic cultures of human renal tumors.
after the treatment period (between 48 and 96 hours)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 16, 2017

Primary Completion (ANTICIPATED)

September 30, 2022

Study Completion (ANTICIPATED)

September 30, 2024

Study Registration Dates

First Submitted

June 15, 2018

First Submitted That Met QC Criteria

June 26, 2018

First Posted (ACTUAL)

June 27, 2018

Study Record Updates

Last Update Posted (ACTUAL)

January 18, 2020

Last Update Submitted That Met QC Criteria

January 16, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC17.063

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Kidney Cancer

Clinical Trials on CK2 and ATM inhibitors serine/ threonin Kinase combination

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ethiopia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe