Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

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

Axitinib

Immunomodulating Agents

Sunitinib

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Programmed death-ligand 1 Inhibitor combined with axitinib

sunitinib or pazopanib

targeted therapy combined with immunotherapy

PD-1 inhibitor combined with axitinib

wei xue

jiwei huang, M.D

wei xue, M.D

Next-Generation Sequencing and whole transcriptome RNA sequencing were used to detect genomic variation and expression in tissues or blood, respectively. The treatment outcome of single targeted therapy or combined with immunotherapy was observed and followed up. Through this study, we intend to achieve RNA molecular classification of Chinese mRCC patients and to evaluate the correlation between ctDNA level, RNA molecular classification and treatment outcome, provide reference for metastatic RCC precise diagnosis and treatment.

Application Circulating Tumor DNA Dynamic Monitoring in Clinical Treatment of Metastatic Renal Cell Carcinoma

A Prospective Observational Study of Molecular Classification and Circulating Tumor DNA Dynamic Monitoring to Explore Related Factors That Predict the Efficacy of Single Targeted Therapy or Combined With Immunotherapy for Metastatic Renal Cell Carcinoma

Ruijin Hospital

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

West China Hospital

Xiangya Hospital of Central South University

Fudan University

Second Affiliated Hospital, School of Medicine, Zhejiang University

Second Affiliated Hospital of Nantong University

Peking University First Hospital

Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University

Shanghai Jiao Tong University Affiliated Sixth People's Hospital

Zhejiang University

First Affiliated Hospital of Wenzhou Medical University

Sir Run Run Shaw Hospital

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

The General Hospital of Eastern Theater Command

The First Affiliated Hospital with Nanjing Medical University

The First Affiliated Hospital of University of Science and Technology of China

The Second Hospital of Anhui Medical University

Tongji Hospital

The First Affiliated Hospital of Zhengzhou University

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Peking Union Medical College Hospital

The First Affiliated Hospital of Shanxi Medical University

Shanxi Provincial Cancer Hospital

Changzhi Medical College

First Affiliated Hospital Xi'an Jiaotong University

Second Affiliated Hospital of Xi'an Jiaotong University

Xijing Hospital of Air Force Military Medical University

Tang-Du Hospital

Quanzhou First Hospital Affiliated to Fujian Medical University

Third Affiliated Hospital, Sun Yat-Sen University

RenJi Hospital

sunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously

Cytoreductive nephrectomy + sunitinib 50 mg orally 4 weeks on/ 2 weeks off or pazopanib 800 mg orally continuously

Cytoreductive nephrectomy and first-line treatment

Cytoreductive nephrectomy

Giuseppe Procopio, MD

Two randomized trials in the cytokine era clearly showed that cytoreductive nephrectomy (CN) had a role in metastatic renal cell carcinoma (mRCC) increasing life expectancy. The survival benefit of tyrosine kinase inhibitors (TKIs) including first-line sunitinib and pazopanib in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy.

Therefore it is unknown if similar survival benefit could be achieved without CN with these new targeted agents.

At the same time there is a need to better understand mechanisms of primary and secondary resistance to TKIs in mRCC patients and to identify eighter prognostic and predictive biomarkers to better define risk factors and potentially druggable targets.

Two randomized trials in the cytokine era clearly showed that CN had a role in mRCC increasing life expectancy. The survival benefit of TKIs including first-line sunitinib and pazopanib in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy.Therefore it is unknown if similar survival benefit could be achieved without CN with these new targeted agents.

At the same time there is a need to better understand mechanisms of primary and secondary resistance to TKIs in mRCC patients and to identify eighter prognostic and predictive biomarkers to better define risk factors and potentially druggable targets.

The hypothesis of this study is that CN followed by TKIs will improve overall survival (OS) when compared to TKIs alone in subjects with mRCC. Circulating blood biomarkers (CBBs) promise to become non-invasive real-time surrogates for tissue-based biomarkers. Circulating tumor cells (CTCs) shed from both primary tumors and metastases, and circulating tumor DNA (ctDNA) released into the bloodstream from dying tumor cells, are likely to capture the entire tumor heterogeneity providing a clear picture of the tumor genetic landscape. Moreover, CTCs fluctuations reflect and possibly anticipate treatment outcome. Through comparison of CBBs before and after disease becomes refractory to therapy, the investigators would be able to address challenging research questions regarding TKIs resistance mechanisms.

This study was designed to compare clinical benefit as measured by Overall Survival (OS), progression-free survival (PFS), overall response rate (ORR) and safety provided by CN followed by TKIs vs upfront TKIs in mRCC subjects.To prospectively collect blood samples from patients at commencement of TKIs therapy and on development of resistance, with the purpose of analyzing CTCs and ctDNA mutational profile to highlight mechanisms underlying TKIs resistance. The investigators additionally aim to assess the role of CTCs as prognostic and pharmacodynamic biomarkers and prospectively collect demographic and clinical outcome data so that molecular and pathological analyses can be measured against clinical endpoints.

Rationale for TKIs treatment choice:

Pazopanib and sunitinib were compared to each other as a therapy for previously untreated patients with mRCC within the phase 3 non inferiority COMPARZ trial which represented the first-ever head-to-head comparison of first-line treatments for mRCC. Overall, the median PFS and OS with pazopanib compared to sunitinib were statistically non-inferior, showing that both agents are active and provide similar high quality care. For this reason the TKI will be assigned based on patients characteristics according to the guidelines of every single institution involved in the study.

Statistical plan:

The sample size was calculated in order to compare 5-year OS between subjects randomized to receive CN followed by TKIs and subjects randomized to receive TKIs (main study endpoint). A total of 191 deaths will yield 80% power to detect a hazard ratio of 1.5 of TKIs vs. CN followed by TKIs with an overall type 1 error of 0.05 (two-sided log-rank test). Such a hazard ratio (HR) corresponds to an increase in the 5-year OS, from an anticipated value 10% for TKIs to 21.5% for CN followed by TKIs. The investigators estimate that approximately 270 patients (135 in each arm), recruited over 3 years and with a minimum follow up of 2 years, will be necessary to see the necessary number of deaths.

An interim analysis of OS based on O'Brien-Fleming stopping rules is planned at 96 deaths at approximately 34 months after randomisation.

Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery

To explore the association between baseline CTCs count and OS or PFS

To compare baseline CTCs count and CTCs at the time of RECIST 1.1 PD on TKIs therapy, with the aim of better understand progressive changes in the tumor as resistance develops

To compare clinical benefit, as measured by Overall Survival (OS), provided by CN followed by TKIs vs upfront TKIs in subjects with mRCC

To compare clinical benefit, as measured by progression-free survival (PFS) and response rate (RR) provided by CN followed by TKIs vs upfront TKIs

Safety profile of cytoreductive nephrectomy with TKIs vs upfront TKIs. (according to Common Terminology Criteria for Adverse Events -CTCAE- v 4.03). All Adverse events will be reported according to National Cancer Institute Criteria. The incidence of adverse events will be summarized according to the primary system-organ class (SOC) and within the category defined in the CTCAE v4.03. The summaries will be overall (severity grades 1-4) and for grade ≥3 events and will also report the actions taken in terms of treatment discontinuation. Similar summaries will be made for serious adverse events. The safety set will be considered.

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Application Circulating Tumor DNA Dynamic Monitoring in Clinical Treatment of Metastatic Renal Cell Carcinoma	NCT05816642	Metastatic Rena...	sunitinib or pa... PD-1 inhibitor ...	-	RenJi Hospital
Targeted Therapy With or Without Nephrectomy in Metastatic Renal Cell Carcinoma: Liquid Biopsy for Biomarkers Discovery	NCT02535351	Clear-cell Meta...	sunitinib or pa... Cytoreductive n...	18 Years - 75 Years	Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Spots Global Cancer Trial Database for sunitinib or pazopanib