Renal Cancer MetastaticBIORENNCT03628859
BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer)
An observational study of Renal Cancer Metastatic, run by Centre Leon Berard at 1 site in France.
Trial summary
The BIOREN project aims are to characterize the genetic background of renal cell carcinomas and their immune environment, to try and identify biomarkers of response and to better understand the mechanisms of resistance to nivolumab in renal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cancer Metastatic
- What is being tested?
- Immunological and tumour characterization
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 21 Dec 2018to Dec 2023
- Phase
- Observational
- 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
Study population: Adult patients presenting a renal metastatic cancer included in Centre Leon Berard for evaluating the mechanisms involved in resistance to immunotherapy: * Cohort 1: ccRCC patients receiving nivolumab, * Cohort 2: ccRCC patients receiving axitinib or cabozantinib or sunitinib or pazopanib, * Cohort 3: ccRCC patients receiving everolimus.
Who may be able to join
- Age ≥ 18 years-old.
- Histology proven locally advanced (unresectable) or metastatic clear cell renal cell carcinoma (mccRCC).
- Starting 2nd or 3rd line of treatment with nivolumab, everolimus, axitinib or cabozantinib as per summaries of product characteristics (SmPC) or 1st line treatment with sunitinib or pazopanib or receiving 2nd or 3rd line of treatment with nivolumab
- Signed informed consent.
Who cannot join
- Psychological, familial, sociological, geographical conditions that would limit compliance with study protocol requirements.
- Pregnant or breastfeeding woman
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Centre Leon Berard
Lyon, 69008
BOYLE Ellen, MD, +33 4.26.55.67.52, helen.boyle@lyon.unicancer.fr
About this study
Official title: BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer) - A Translational Study on Immunotherapy for Metastatic Renal Cancer
The BIOREN project aims are to characterize the genetic background of renal cell carcinomas and their immune environment, to try and identify biomarkers of response and to better understand the mechanisms of resistance to nivolumab in renal cancer.
Read the detailed description
Around 338,000 new cases of renal cell carcinoma (RCC) are diagnosed worldwide per year (1). RCC is one of the most immune responsive human cancers. For a long time the only available treatment were high-dose IL-2 and IFN-α with only a few patients achieving durable responses. Clinical trials conducted in the past 15 years have led to the approval of several anti-angiogenic treatments, mainly vascular endothelial growth factor receptor (VEGFR) inhibitors and mTOR inhibitors. Currently most patients receive first line anti-VEGF therapy.
Recently a better understanding of the mechanisms by which tumours evade the immune system has led to the development of checkpoint inhibitors, such as anti CTLA-4, anti-PD-1 and anti-PD-L1 antibodies that have been tested in various tumour types.
Recently, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved the human IgG4 anti-PD1 monoclonal antibody, nivolumab, for advanced/metastatic clear cell RCC (ccRCC) patients who have received prior antiangiogenic therapy. PD-1 is a key immune-checkpoint receptor (ICR) expressed by activated T cells, which mediates immunosuppression primarily in peripheral tissues, where T cells may encounter the immunosuppressive PD-1 ligands, PD-L1 (B7-H1) and PD-L2(B7-DC) on tumour cells, stromal cells or both.
Despite encouraging results, the clinical response to anti-PD1 is not as wide as expected and there are not any biomarkers 1) that are able to predict which patients will respond and 2) that predict response to nivolumab in patients with ccRCC.
BIOREN is a translational, prospective, observational 3-cohort study.
The aims of BIOREN are to characterize the genetic background of the tumours and also their immune environment, to try and identify biomarkers of response and to better understand the mechanisms of resistance to nivolumab in renal cancer. We will focus on:
- Tregs function and modulation of function,
- NK cells known to be regulated by nivolumab,
- The biological rationale for coupling CXCR4 antagonist with anti PD-1 therapy, analysed with mice models,
- To try to identify biomarkers of response by further characterization of the tumours and evaluating the immune status.
The project will enrol patients receiving in 2nd or 3rd line treatment for metastatic ccRCC: Nivolumab but also, as control cohorts, either everolimus or axitinib (approved treatments in this setting), as well as cabozantinib in France (recently approved in 2nd or 3rd line).
French blood samples and archival FFPE (formalin-fixed paraffin embedded) specimens will be analysed in in France, and also sent to the partners of the Transcan project Consortium (Israel, Italy and Spain).
- Conditions
- Renal Cancer Metastatic
- Being tested
- Immunological and tumour characterization
- Keywords
- Renal cancer metastatic, Immunotherapy, Predictive biomarkers, Translational study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunological and tumour characterizationBiological
FFPE, blood samples (liquid biopsy, heparin and EDTA blood) performed in patients presenting a renal metastatic cancer receiving treatment as standard practice according to physician's choice (2nd or 3rd line of treatment with nivolumab, everolimus, axitinib or cabozantinib [in France only], as per product SmPC or 1st line treatment with sunitinib or pazopanib or receiving 2nd or 3rd line of treatment with nivolumab)
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Tregs function on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment
Ex vivo effect of CXCR4 antagonists (PCT/IB2011/000120/ EP2528936B1/ US2013/0079292A1) and other Tregs targets antagonists (ICOS, CD39/CD73) or agonists (TLR7L) as putative anti-PD1 resistance mechanisms
Measured: Evolution of percentage of CD4+CD25+ CD127low FOXP3+ cells between inclusion and up to 24 months
Secondary outcomes (4)
Evaluation of NK function/cytotoxicity on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment
NK cytotoxicity will be evaluated through NK cell degranulation (CD107a assay), intracellular staining of the lytic proteins, Grz A and GrzB and intracellular cytokines, GM-CSF, IFNγ, IL-10, TNF. NK cell will be characterized for CXCR4; maturation markers: CD16, CD56, CD57, CD62L, NKG2A; activating receptors markers: CD25, CD69, NKp44, NKp30, NKp46, NKG2D. Ex vivo effect of CXCR4 antagonists on NK cytotoxicity.
Measured: Evolution between inclusion and up to 24 months
Exploration of the biological rationale for coupling CXCR4 antagonist with anti-PD-1 in in vivo models of renal cancer (mice models).
immunocompetent model (RENCA), human xenograft model (786 cell) and humanized model
Measured: Up to 24 months
Identification of response biomarkers
Characterization of the tumours using different techniques (RNASeq whole genome, NGS analysis, IHC, HTG focus RNAseq)
Measured: Up to 24 months
Identification of biomarkers of response
Immune status (Multi-IF analysis, TCR sequencing and clonality analysis, Anti-HERV T cell and humoral response)
Measured: Evolution between inclusion and up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2018
- Study start21 Dec 2018
- Primary completionJun 2023 (estimated)
- Study completionDec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Centre Leon BerardThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Leon Berard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- BOYLE J Helen, MD, Principal investigator, Centre Leon Berard
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03628859
- Sponsor's protocol ID
- BIOREN (ET18-017)
- Acronym
- BIOREN
- Status last verified
- Mar 2022
- First submitted
- 28 Mar 2018
- Last updated
- 15 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer) - A Translational Study on Immunotherapy for Metastatic Renal Cancer
- ClinicalTrials.gov ID
- NCT03628859
- Acronym / sponsor ID
- BIOREN / BIOREN (ET18-017)
- Conditions
- Renal Cancer Metastatic
- Keywords
- Renal cancer metastatic, Immunotherapy, Predictive biomarkers, Translational study
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Centre Leon BerardUniversity, hospital or other
- Study start
- 21 Dec 2018 (actual)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Dec 2023 (estimated)
- First posted
- 14 Aug 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 BIOREN project aims are to characterize the genetic background of renal cell carcinomas and their immune environment, to try and identify biomarkers of response and to better understand the mechanisms of resistance to nivolumab in renal cancer.
Detailed description
Around 338,000 new cases of renal cell carcinoma (RCC) are diagnosed worldwide per year (1). RCC is one of the most immune responsive human cancers. For a long time the only available treatment were high-dose IL-2 and IFN-α with only a few patients achieving durable responses. Clinical trials conducted in the past 15 years have led to the approval of several anti-angiogenic treatments, mainly vascular endothelial growth factor receptor (VEGFR) inhibitors and mTOR inhibitors. Currently most patients receive first line anti-VEGF therapy.
Recently a better understanding of the mechanisms by which tumours evade the immune system has led to the development of checkpoint inhibitors, such as anti CTLA-4, anti-PD-1 and anti-PD-L1 antibodies that have been tested in various tumour types.
Recently, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved the human IgG4 anti-PD1 monoclonal antibody, nivolumab, for advanced/metastatic clear cell RCC (ccRCC) patients who have received prior antiangiogenic therapy. PD-1 is a key immune-checkpoint receptor (ICR) expressed by activated T cells, which mediates immunosuppression primarily in peripheral tissues, where T cells may encounter the immunosuppressive PD-1 ligands, PD-L1 (B7-H1) and PD-L2(B7-DC) on tumour cells, stromal cells or both.
Despite encouraging results, the clinical response to anti-PD1 is not as wide as expected and there are not any biomarkers 1) that are able to predict which patients will respond and 2) that predict response to nivolumab in patients with ccRCC.
BIOREN is a translational, prospective, observational 3-cohort study.
The aims of BIOREN are to characterize the genetic background of the tumours and also their immune environment, to try and identify biomarkers of response and to better understand the mechanisms of resistance to nivolumab in renal cancer. We will focus on:
- Tregs function and modulation of function,
- NK cells known to be regulated by nivolumab,
- The biological rationale for coupling CXCR4 antagonist with anti PD-1 therapy, analysed with mice models,
- To try to identify biomarkers of response by further characterization of the tumours and evaluating the immune status.
The project will enrol patients receiving in 2nd or 3rd line treatment for metastatic ccRCC: Nivolumab but also, as control cohorts, either everolimus or axitinib (approved treatments in this setting), as well as cabozantinib in France (recently approved in 2nd or 3rd line).
French blood samples and archival FFPE (formalin-fixed paraffin embedded) specimens will be analysed in in France, and also sent to the partners of the Transcan project Consortium (Israel, Italy and Spain).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients presenting a renal metastatic cancer included in Centre Leon Berard for evaluating the mechanisms involved in resistance to immunotherapy: * Cohort 1: ccRCC patients receiving nivolumab, * Cohort 2: ccRCC patients receiving axitinib or cabozantinib or sunitinib or pazopanib, * Cohort 3: ccRCC patients receiving everolimus.
Key inclusion criteria (4 listed)
- Age ≥ 18 years-old.
- Histology proven locally advanced (unresectable) or metastatic clear cell renal cell carcinoma (mccRCC).
- Starting 2nd or 3rd line of treatment with nivolumab, everolimus, axitinib or cabozantinib as per summaries of product characteristics (SmPC) or 1st line treatment with sunitinib or pazopanib or receiving 2nd or 3rd line of treatment with nivolumab
- Signed informed consent.
Key exclusion criteria (2 listed)
- Psychological, familial, sociological, geographical conditions that would limit compliance with study protocol requirements.
- Pregnant or breastfeeding woman
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 |
|---|---|---|
| Immunological and tumour characterizationFFPE, blood samples (liquid biopsy, heparin and EDTA blood) performed in patients presenting a renal metastatic cancer receiving treatment as standard practice according to physician's choice (2nd or 3rd line of treatment with nivolumab, everolimus, axitinib or cabozantinib [in France only], as per product SmPC or 1st line treatment with sunitinib or pazopanib or receiving 2nd or 3rd line of treatment with nivolumab) | Biological | – |
Primary outcome
Evaluation of Tregs function on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment
Time frame: Evolution of percentage of CD4+CD25+ CD127low FOXP3+ cells between inclusion and up to 24 months
Ex vivo effect of CXCR4 antagonists (PCT/IB2011/000120/ EP2528936B1/ US2013/0079292A1) and other Tregs targets antagonists (ICOS, CD39/CD73) or agonists (TLR7L) as putative anti-PD1 resistance mechanisms
4 secondary outcomes
Evaluation of NK function/cytotoxicity on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment
Time frame: Evolution between inclusion and up to 24 months
Exploration of the biological rationale for coupling CXCR4 antagonist with anti-PD-1 in in vivo models of renal cancer (mice models).
Time frame: Up to 24 months
Identification of response biomarkers
Time frame: Up to 24 months
Identification of biomarkers of response
Time frame: Evolution between inclusion and up to 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
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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.
BOYLE J Helen, MD principal investigator
Centre Leon Berard
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Renal Cancer Metastatic, run by Centre Leon Berard 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 4 inclusion and 2 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 15 Mar 2022. 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 BLANC Ellen (+33 4.78.78.29.67, ellen.blanc@lyon.unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of Tregs function on peripheral blood/neoplastic tissue from mRCC patients undergoing nivolumab treatment (time frame: Evolution of percentage of CD4+CD25+ CD127low FOXP3+ cells between inclusion and up to 24 months). 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 15 Mar 2022.