Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Hypofractionated radiation will be administered to a metastatic disease site at a dose and schedule of 30 Gy in 3 consecutive fractions. The day of first administration of Nivolumab will be designated as Time 1. Nivolumab will be given as flat dose of 240 mg in intravenous infusion beginning on day 1 every 14 days for 6 months, than switch to 480 mg q4-weekly in responding (CR, PR, SD) patients until PD or unacceptable toxicity .

SRT will be administered between the first and second administration of Nivolumab (7 days after the first infusion of Nivolumab).

Carmine Pinto, MD

NIVES study is an ongoing phase II, single arm, multicenter study. In this trial pts received SBRT to one non-brain measurable lesion and concomitant NIVOLUMAB, an anti-programmed cell death (PD-1). Combining SBRT with NIVO may enhance the antitumor immune responses and improve clinical outcomes, how it was demonstrated for other solid tumors with a phenomenon known as the abscopal effect . It was planned to enrolled a total of 68 pts within 12 months. The objective of the current analysis is to describe the first report of safety profile of NIVO in combination with SBRT.

Nivolumab Plus Stereotactic Body Radiotherapy in II and III Line of Patients With Metastatic Renal Cell Carcinoma

Nivolumab Plus Stereotactic Body Radiotherapy (SBRT) in II and III Line of Patients With Metastatic Renal Cell Carcinoma (mRCC)

Immune checkpoint inhibitors act by shortcutting the communication between immune cells and tumor cells mediated by the PD1-PDL1 interaction. Discordant results about the correlation of PDL1 expression and response to immunotherapy exist. Thus, we will investigate the expression of PDL1 in the tumor using four available IHC test (Dako 28.8, Dako 22C3, Ventana SP142, Ventana SP 263) and we will correlate levels of expression with response to treatment.

To evaluate whether and how the initial genetic background of the renal carcinoma may impact on response to treatment in the present setting a deep sequencing analysis will be performed to assess mutational status of 578 cancer genes using the Comprehensive Cancer Design panel (Roche) and MySeq Illumina Next Generation Sequencer. The overall mutations load and the type of mutations detected will be correlated with the response to treatment.

To investigate the effect of stereotactic radiotherapy on the modulation of the immune system we propose to analyze variation in the plasma levels of soluble immune-modulators during treatment. Will be use the Bio-Plex Pro™ Human Inflammation Assay (Bioplex, Biorad) that enables to detect and quantify a panel of 24 key biomarkers of inflammation including TNF superfamily proteins, IFN family proteins, and Treg cytokines

we will investigate JAK1, JAK2 and B2M mutations by in the circulating free tumor DNA (ctDNA) obtained from the plasma samples. The ctDNA will be analyzed with a multiplexed sequencing assay that generates reads containing targeted regions along with a molecular tag that allows the accompanying optimized variant analysis software to assemble the reads into families of molecules originating from the same initial ctDNA molecules and model errors accumulated during library amplification, templating, and sequencing to accurately reconstruct the sequence of the original ctDNA molecule. The resulting sequence is then used to make variant calls down to 0.05% allele ratio with high sensitivity and specificity.

Objective Response Rate (ORR) , as determined by investigator assessment per RECIST 1.1 Secondary as determined by investigator assessment per RECIST 1.1

the time between the date of registration and the first date of documented progression, based on invesigator assessment (as per RECIST 1.1 criteria), or death due to any cause, whichever occurs first

the time from registration to the date of death from any cause

determined by investigator assessment per RECIST 1.1

All Adverse Events (AEs) and laboratory abnormalities will be collected and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03

Gruppo Oncologico Italiano di Ricerca Clinica

Amino Acids

Angiogenesis Inhibitors

Immunomodulating Agents

Tyrosine Kinase Inhibitors

Tyrosine

Therapeutic combination tyrosine kinase inhibitor (TKI) + immune checkpoint inhibitors (ICI)

Therapeutic combination with different immune checkpoint inhibitors (ICI)

Systematic extra blood sampling at inclusion, 6 weeks after inclusion and in case of progression of the cancer

Blood collection

reuse of tumour tissue collect in usual patient care

Tumour samples

Natacha Nohilé

Laetitia MAUGE, PharmD, PhD

Marie AUVRAY-KUNITZ, MD

Olivier HUILLARD, MD

Olivier HUILLARD, MD, PhD

This is a multicenter, exploratory, prospective study to identify angiogenesis and immune-related biomarkers predictive of progression free survival in patients with metastatic or advanced renal cell carcinoma treated by a combination of immunotherapy and antiangiogenic.

Recently, the management of renal cell carcinoma has undergone major changes with the emergence of combined therapies associating tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) as first line treatments. However, there are no criteria to guide the choice between the different combinations validated and or between ICI combinations. Angiogenesis and immunity are intimately linked and some markers related have could be interesting to predict the efficacy of these combinations. Angiogenesis and immunity are highly related. This link may lead to new biomarkers to be explored to predict the response to TKI + ICI therapy combinations. On this basis, the investigators propose to conduct an open-label exploratory, multicenter prospective trial to study the association between angiogenesis and immune markers and the effect of combined TKI+ICI treatments.

Biomarkers of Angiogenesis for Response to Therapeutic Combination in Advanced or Metastatic Kidney Cancer

Predictive Role of Circulating Biomarkers Involved in Angiogenesis in Metastatic Kidney Cancer in the Era of New Therapeutic Associations: Immunotherapies, Anti-angiogenic

Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared

Time from inclusion to progression documented by imaging and based on RECIST 1.1 and iRECIST criteria or patient death. The iRECIST criteria use the same methods of monitoring tumor lesions as the RECIST 1.1 criteria but a confirmation 4-6 weeks after suspicion of progression is required to confirm or rule out progression because patients undergoing immunotherapy may present pseudo-progressions.

Observation of a partial or complete response according to RECIST 1.1 criteria during the follow-up

Time between the observation of an objective response (partial or complete according to RECIST 1.1 criteria) and the progression

Institut National de la Santé Et de la Recherche Médicale, France

FONCER contre le cancer

Assistance Publique - Hôpitaux de Paris

Antibodies

Tin Fluorides

Ipilimumab

Immunoglobulins

Nivolumab IV 3mg/kg 3/3w + Ipilimumab 1mg/kg 3/3w 4 doses, followed by Nivolumab IV 480mg 4/4w until progression, toxicity, or up to 2 years of use.

Nivolumab is called an anti-PD-1 (Programmed Cell Death Ligand 1) or a checkpoint inhibitor and is an antibody (a type of human protein) designed to allow the body's own immune system to destroy tumors

Ipilimumab is called an anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and is a type of antibody that works to prevent the body's immune system from stopping to fight a specific cancer

Leandro Machado Colli, MD, PhD

Matheus Aquino Guimarães, MD, Msc

Leandro Colli

Rodolfo Borges Reis, MD, PhD

The study is studying the joint contribution and interactions of germline variants and somatic mutations and their impact on Renal Cell Carcinoma (RCC) development and treatment (immunotherapy).

One hundred newly diagnosticated stage IV RCC patients will be recruited in the Ribeirao Preto Medical School.

Patients will be treated with immune checkpoint inhibitors (ICI) combination: nivolumab (3 mg/kg of body weight) plus ipilimumab (1 mg/kg) intravenously every three weeks for four doses, followed by nivolumab 480mg every four weeks, until progression, toxicity or complete two years of treatment.

Patients will be followed up for the clinical outcome (progression-free survival, best response, and overall survival).

Fresh-frozen primary tumor tissue will be collected for somatic genomic characterization.

Blood DNA will be genotyped for the identification of common germline variation, as well as ancestry determination.

CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy

CLARA: Characterization of Somatic and Germline Mechanisms That Impact the Immunotherapy Treatment and Prognosis of Patients With Renal Cancer

The research team is committed to sharing data generated by this project with the research community. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement.

Bristol-Myers Squibb

Fundação de Amparo à Pesquisa do Estado de São Paulo

Hospital das Clínicas de Ribeirão Preto

Head of Oncology

Fibrinolytic Agents

Anticoagulants

Everolimus

Axitinib

Heparin

Sunitinib

Calcium heparin

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)

Immunological and tumour characterization

BLANC Ellen

BOYLE J Helen, MD

BOYLE Ellen, MD

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.

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).

Archival FFPE specimen

Blood samples performed during standard visits and not requiring additional blood tests:

* Heparin blood (4 x 6ml)
* EDTA blood (5 x 6ml)
* Liquid biopsy (EDTA) (5 x 6ml)

BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer)

BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer) - A Translational Study on Immunotherapy for Metastatic Renal Cancer

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

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.

immunocompetent model (RENCA), human xenograft model (786 cell) and humanized model

Characterization of the tumours using different techniques (RNASeq whole genome, NGS analysis, IHC, HTG focus RNAseq)

Immune status (Multi-IF analysis, TCR sequencing and clonality analysis, Anti-HERV T cell and humoral response)

Centre Leon Berard

Pembrolizumab

Drug: Axitinib 5mg orally twice a day Combination Treatment：Anti-PD-1 Combinations of D-CIK Immunotherapy

Autologous dendritic and cytokine-induced killer cells (D-CIK)(1.0-1.5\*10\^10 cells)were incubated with low dose anti-PD-1 antibody（pembrolizumab, Merck \& Co., Inc.） and were transferred to participants via intravenous infusion .

Combinations treatment

Fangjian Zhou, MD.PhD

Fang-Jian Zhou, M.D Ph.D

Zhi-Ling Zhang, M.D Ph.D

Jian-Chuan Xia, Ph.D

Phase II clinical trial to investigate the safety, clinical activity and toxicity of combinations of D-CIK and low dose anti-PD-1 antibody in patients with metastatic renal cell carcinoma treated with axitinib.

This is a phase II, single arm study to investigate the safety and efficacy of pembrolizumab-activated autologous D-CIK cells (CIK:Cytokine-induced killer, D-CIK:CIK cells are stimulated using mature dendritic cells) with Axitinib in patients with advanced kidney cancer.

Heparinized peripheral blood was obtained from participants over a 1-week period. PBMCs(Peripheral blood mononuclear cells) were separated by Ficoll-Hypaque gradient centrifugation, suspended in X-VIVO 15 serum-free medium, and culture with 1000 U/ml rhIFN-γfor the first 24 h, followed by stimulation with 100 ng/ml OKT-3 , 1000 U/ml rhIL-2 and 100 U/ml IL-1α to activate the CIK.Dendritic cells were incubated with CIK. Fresh medium containing 1000 U/ml rhIL-2 was added every 2 days and the cell density was maintained at 2×10\^6 cells/mL.D-CIK were harvested, washed, and resuspended after culture for 14 days. Before cell transfer,D-CIK were incubated with anti-PD-1 antibody(Pembrolizumab (Merck \& Co., Inc.) is a humanized IgG4 anti-PD-1 monoclonal antibody that binds to PD-1 to prevent it from engaging with PD-L1 or PD-L2.), and a fraction of the D-CIK were collected to assess their number, phenotype, and viability of cells, and to test for possible contamination by bacteria, fungi, or endotoxins. Then, autologous D-CIK (1.0-1.5\*10\^10 cells) were transferred to patients via intravenous infusion.

The present study was designed with Simon's best two stage study to explore the efficacy and safety of low-dose pembrolizumab in the treatment of patients with advanced renal cancer by D-CIK re-transfusion combined with Axitinib in vitro. The expected effective rate of the combined treatment is set at 60%, and if the effective rate is less than 30%, the effective rate of the combined treatment is considered to be at an undesirable level. The best two-stage design is 3/8, 10/24. In the first stage, 8 patients need to be treated. If the number of effective cases is less than 3, the combined treatment is deemed ineffective and the trial needs to be terminated. If the number of effective cases is more than 3, the phase II trial will be continued, and a total of 24 subjects need to be included.

Autologous D-CIK (1.0-1.5\*10\^10 cells) will be transferred to patients via intravenous infusion. Before cell transfer, D-CIK were incubated with anti-PD-1 antibody.

A Study of Anti-PD-1 Combinations of D-CIK Immunotherapy and Axitinib in Advanced Ranal Carcinoma

A Study of Anti-PD-1( Pembrolizumab) Combinations of D-CIK (Cytokine-induced Killer Cells Are Stimulated Using Mature Dendritic Cells) Immunotherapy and Axitinib in Advanced Ranal Carcinoma

We did not decide whether to share the subject's personal information

The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib,will be assessed using irRC and RECIST 1.1 to determine tumor response.

The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using irRC and RECIST 1.1 to determine progression-free survival time.

The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using irRC and RECIST 1.1 to determine overall survival time.

The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using irRC and RECIST 1.1 to determine duration of response.

The treatment effect of Anti-PD-1 combinations of D-CIK immunotherapy and axitinib, will be assessed using EQ-5D-5L and NCCN-FACT FKSI-19 v2.0.to determine the quality of life.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab Plus Stereotactic Body Radiotherapy in II and III Line of Patients With Metastatic Renal Cell Carcinoma	NCT03469713	Renal Cancer Me...	Nivolumab	18 Years -	Gruppo Oncologico Italiano di Ricerca Clinica
Biomarkers of Angiogenesis for Response to Therapeutic Combination in Advanced or Metastatic Kidney Cancer	NCT05285579	Renal Cell Carc... Renal Cancer Renal Cancer Me...	Blood collectio... Tumour samples	18 Years -	Assistance Publique - Hôpitaux de Paris
CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy	NCT05215470	Renal Cancer Me...	Nivolumab Ipilimumab	18 Years -	Hospital das Clínicas de Ribeirão Preto
BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer)	NCT03628859	Renal Cancer Me...	Immunological a...	18 Years -	Centre Leon Berard
Nivolumab Plus Stereotactic Body Radiotherapy in II and III Line of Patients With Metastatic Renal Cell Carcinoma	NCT03469713	Renal Cancer Me...	Nivolumab	18 Years -	Gruppo Oncologico Italiano di Ricerca Clinica
BIOREN (Predictive BIOmarkers in Metastatic RENal Cancer)	NCT03628859	Renal Cancer Me...	Immunological a...	18 Years -	Centre Leon Berard
A Study of Anti-PD-1 Combinations of D-CIK Immunotherapy and Axitinib in Advanced Ranal Carcinoma	NCT03736330	Renal Cancer Me...	Combinations tr...	-	Sun Yat-sen University

Spots Global Cancer Trial Database for renal cancer metastatic