Kidney CancerCOMBOREINNCT03571438
Evaluation of a Promising New Combination of Protein Kinase Inhibitors on Organotypic Cultures of Human Renal Tumors
A study testing CK2 and ATM inhibitors serine/ threonin Kinase combination, Sunitinib and Pazopanib in people with Kidney Cancer, run by University Hospital, Grenoble at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Cancer
- What is being tested?
- CK2 and ATM inhibitors serine/ threonin Kinase combination, Sunitinib and Pazopanib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 16 Oct 2017to 30 Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Grenoble Alps Hospital
Grenoble, 38043
Jean-Luc Descotes, PU-PH
About this study
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.
Read the 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.
- Conditions
- Kidney Cancer
- Being tested
- CK2 and ATM inhibitors serine/ threonin Kinase combination, Sunitinib, Pazopanib, Temsirolimus
- Medical subject headings
- Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CK2 and ATM inhibitors serine/ threonin Kinase combinationCombination product
Treatment of cell culture with CK2 and ATM inhibitors serine/ threonin Kinase combination
SunitinibDrug
Treatment of cell culture with Sunitinib
PazopanibDrug
Treatment of cell culture with Pazopanib
TemsirolimusDrug
Treatment of cell culture with Temsirolimus
| Study group | Role | What they receive |
|---|---|---|
| CK2(CX4945) and ATM(Ku 60019) | Experimental | Treatment of cell culture with a combination of CK2 and ATM inhibitors serine/ threonin Kinase combination Receives: Combination Product: CK2 and ATM inhibitors serine/ threonin Kinase combination |
| Sunitinib | Active comparator | Treatment of cell culture with Sunitinib Receives: Drug: Sunitinib |
| Pazopanib | Active comparator | Treatment of cell culture with Pazopanib Receives: Drug: Pazopanib |
| Temsirolimus | Active comparator | Treatment of cell culture with Temsirolimus Receives: Drug: Temsirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of cell death on organotypic cultures of human renal tumors (Efficacy)
Death cell rate on organotypic cultures of human renal tumors.
Measured: after the treatment period (between 48 and 96 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2018
- Study start16 Oct 2017
- Primary completion30 Sep 2022 (estimated)
- Study completion30 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03571438
- Sponsor's protocol ID
- 38RC17.063
- Acronym
- COMBOREIN
- Status last verified
- Jan 2020
- First submitted
- 15 Jun 2018
- Last updated
- 18 Jan 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of a Promising New Combination of Protein Kinase Inhibitors on Organotypic Cultures of Human Renal Tumors
- ClinicalTrials.gov ID
- NCT03571438
- Acronym / sponsor ID
- COMBOREIN / 38RC17.063
- Conditions
- Kidney Cancer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- 16 Oct 2017 (actual)
- Primary completion
- 30 Sep 2022 (estimated)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 27 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CK2(CX4945) and ATM(Ku 60019) | Experimental | Combination Product: CK2 and ATM inhibitors serine/ threonin Kinase combinationTreatment of cell culture with a combination of CK2 and ATM inhibitors serine/ threonin Kinase combination |
| Sunitinib | Active comparator | Drug: SunitinibTreatment of cell culture with Sunitinib |
| Pazopanib | Active comparator | Drug: PazopanibTreatment of cell culture with Pazopanib |
| Temsirolimus | Active comparator | Drug: TemsirolimusTreatment of cell culture with Temsirolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CK2 and ATM inhibitors serine/ threonin Kinase combinationTreatment of cell culture with CK2 and ATM inhibitors serine/ threonin Kinase combination | Combination product | CK2(CX4945) and ATM(Ku 60019) |
| SunitinibTreatment of cell culture with Sunitinib | Drug | Sunitinib |
| PazopanibTreatment of cell culture with Pazopanib | Drug | Pazopanib |
| TemsirolimusTreatment of cell culture with Temsirolimus | Drug | Temsirolimus |
Primary outcome
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CK2 and ATM inhibitors serine/ threonin Kinase combination, Sunitinib and Pazopanib in people with Kidney Cancer, run by University Hospital, Grenoble at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean-Luc Descotes, PU-PH (+33 (0)4 76 76 59 22, jldescotes@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of cell death on organotypic cultures of human renal tumors (Efficacy) (time frame: after the treatment period (between 48 and 96 hours)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.