Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Multiple Primary

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

Ipilimumab

Surgery after induction therapy with IO/IO or a TKI/IO-combination, followed by maintenance therapy with nivolumab or a TKI/IO-combination.

Induction therapy wih IO/IO or a TKI/IO-combination, followed by maintenance therapy with nivolumab or a TKI/IO-combination.

Partial or complete nephrectomy by open, laparoscopic, or robotic approach.

Cytoreductive nephrectomy

Tumor biopsies, blood, and stool specimens for translational biomarker research will be sampled at baseline and after 3 or 6 months.

Tissue sampling

Niels Fristrup, MD PhD

Anne Kirstine Moeller, MD, PhD

Niels Viggo Jensen, MD

BACKGROUND: For synchronous metastatic renal cell carcinoma (RCC), surgical resection of the primary tumor in the presence of distant metastases has been the standard of therapy for select patients followed by systemic therapy. In the era of TKIs two randomized trials, CARMENA and SURTIME, have questioned the role and timing of surgery in these patients, results point towards no surgery or a deferred approach.

RATIONALE: The antitumor activity of immune checkpoint blockage (ICB) is more potent than other therapy in mRCC. The deferred cytoreductive nephrectomy approach ensures systemic therapy for all patients, avoid systemic treatment delay, and spare surgery in patients with progressive tumors. Current data only point towards a survival benefit for cytoreductive nephrectomy in intermediate risk patients, but not in poor risk patients

HYPOTHESIS: Deferred cytoreductive nephrectomy after initial nivolumab combined with ipilimumab or a TKI/IO-combination will improve OS in patients with synchronous metastatic RCC and ≤3 IMDC risk features

This is an open, randomized, multicenter comparison trial, designed to evaluate the effect of deferred cytoreductive nephrectomy compared with no surgery following initial nivolumab combined with ipilimumab or a TKI-combination, in mRCC patients with IMDC intermediate and poor risk.

OUTLINE: This is a multicenter trial, patients are stratified according to institution, treatment choice, number of IMDC risk factors, and combined elevated neutrophil-lymphocyte ratio and hyponatremia.

All patients will receive induction checkpoint immunotherapy immediately after inclusion. After 3 months or a total of 4 series of nivolumab combined with ipilimumab or a TKI/IO-combination, the patient will be discussed for resectability at the multidisciplinary meeting (MDT). Whether the patient is eligible for cytoreductive nephrectomy is at the discretion of the urologist at the local MDT. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy will then undergo randomization. Patients deemed not suitable for surgery or have \> 3 IMDC risk features at the 3 month evaluation continue systemic therapy for 3 months, followed by a 2nd evaluation. Patients with ≤ 3 IMDC risk factors and deemed suitable for cytoreductive nephrectomy at 2nd evaluation will then undergo randomization. Patients deemed not suitable for surgery or have \> 3 IMDC risk features at the 6 month evaluation continue systemic therapy. Nivolumab may continue until unacceptable toxicity or total treatment length of 2 years from inclusion.

ARM A: Deferred cytoreductive nephrectomy, followed by maintenance nivolumab or a TKI/IO-combination.

ARM B: No surgery, receive maintenance nivolumab or a TKI/IO-combination.

Patients undergo tumor tissue, blood, and stool collection at baseline, 3 and 6 months, for planned translational research.

Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-Trial

Multicenter Randomized Trial of Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma Receiving Checkpoint Inhibitors: a DaRenCa and NoRenCa Trial Evaluating the Impact of Surgery or No Surgery. The NORDIC-SUN-Trial

Calculated from the date of inclusion, to the date of death of any cause or censored at the date at last follow-up.

Calculated from date of inclusion to date of initiation of subsequent therapy or death of any cause or censored at the date of last follow-up

Aarhus University Hospital

Niels Fristrup

MD PhD

Cytoreductive nephrectomy±metastasectomy, followed by induction therapy with nivolumab plus ipilimumab combination and maintenance therapy with nivolumab.

Cytoreductive nephrectomy±metastasectomy after induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab.

Induction therapy with nivolumab plus ipilimumab combination, followed by maintenance therapy with nivolumab.

Partial or complete nephrectomy by open, laparoscopic, or robotic approach and/or metastasectomy Tumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, surgery, after induction therapy, and after 3 months of maintenance therapy.

Cytoreductive nephrectomy±metastasectomy

Tumor tissue, blood, urine and stool specimens for translational biomarker research will be sample at baseline, after induction therapy, and after 3 months of maintenance therapy.

Human-derived materials sampling

Won Sik Ham

Kang Su Cho

Jongchan Kim

BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been questioned and remains undetermined in the immuno-oncology era. Results from the two randomized trials, CARMENA and SURTIME, have questioned the role and timing of the surgery in these patients, however, these trials have only used the targeted therapy, sunitinib. With the advent of more effective systemic therapies including immune checkpoint inhibitors (ICIs), the role of surgical therapy should be reexamined.

RATIONALE: The therapeutic effects of ICIs have demonstrated improved oncological outcomes compared to sunitinib. The updated results reported the beneficial role of upfront and deferred CN approach for selected patients. No studies have formally investigated the role of CN in the immune-oncology era where combinatorial use of CN plus ICIs might be beneficial.

HYPOTHESIS: Upfront or deferred CN will improve oncological outcomes (overall survival, and progression free survival) in patients with synchronous mRCC and ≤3 IMDC risk features compared to immune checkpoint inhibitors (nivolumab plus ipilimumab combination) alone.

This is an open, randomized, multicenter comparison trial, designed to evaluate the effect of the potential role of CN in combination with immunotherapy in mRCC patients with IMDC intermediate and poor risk.

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial

By Common Terminology Criteria for Adverse Events version 5.0

Assessed according to the Clavien-Dindo classification of surgical complications

Measured by flowcytometry at baseline and after surgery and/or after ICIs compared with OS, PFS, ORR

Measured by Next generation sequencing (NGS) methods compared with OS, PFS, and ORR

Measured by NGS methods compared with OS, PFS, and ORR

Evaluate the microbiome composition measured by NGS methods compared with OS, PFS, and ORR

Yonsei University

Infections

Digestive System Diseases

Symptoms and General Pathology

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Esophageal Neoplasms

Communicable Diseases

Oropharyngeal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Disease Attributes

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Esophageal Cancer

patients aged ≥ 20 years with esophageal cancer

patients aged ≥ 20 years with oropharyngeal cancer

patients aged ≥ 20 years with synchronous oropharyngeal cancer and esophageal cancer

patients aged ≥ 20 years with symptoms of dysphagia without cancer

In this study, we will perform tissue biopsy at esophageal tumor site in esophageal cancer patients and perform random biopsy at middle esophagus in patients without esophageal cancer. Besides, we will take oral swab in all participants.

Oral swab test

Hsueh-Chien Chiang, M.D.

Jenn-Wei Chen, Ph.D

Hsueh-Chien Chiang

Wei-Lun Chang, M.D. Ph.D

Background: Esophageal cancer commonly occurs in middle-aged man. It is ranked to the 6th common cancer and 5th cancer-related death in Taiwanese male, and sometimes co-exist with oropharyngeal cancer, which impacts our national economics and productivity a lot. To improve the prognosis of esophageal cancer, we should contribute to early diagnosis and improved treatment of the disease. Recent studies showed oral and esophageal dysbiosis may lead to oropharyngeal and esophageal cancer.

Aim: To investigate whether oral microbiota is similar to esophageal microbiota. To investigate whether oral microbiota can be a non-invasive biomarker of oropharyngeal cancer, esophageal cancer, synchronous cancer and chemoradiation resistance. And whether probiotic supplement can improve oral/esophageal dysbiosis in order to prevent esophageal cancer.

Study design: This study compares the oral/esophageal microbiota composition between oropharyngeal cancer cases, esophageal cancer cases, synchronous cancer cases and non-cancer controls. In addition, the link between oral and esophageal microbiota will be explored. The study will identify the microbiota related with esophageal cancer development. We will also validate the effect of probiotic supplementation on improving oral/esophageal dysbiosis.

Expected result and significance: Examination of oral microbiota has the potential to become a non-invasive tool for oropharyngeal cancer, esophageal cancer, and synchronous cancer. Probiotic supplementation has the potential to improve oral dysbiosis.

Esophageal cancer is one of the most common gastrointestinal malignant diseases worldwide with an estimated 456,000 incident cases annually. Esophageal cancer has a poor prognosis and high mortality rate. The 5-year survival rate is around 15%-25%. The treatment options of esophageal cancer can be divided into curative treatment and palliative treatment, while endoscopy, surgery and chemoradiotherapy were involved. However, 60-70% patients diagnosed with esophageal cancer are not eligible for curative treatment. In these patients, chemoradiotherapy is the standard for unresectable esophageal cancer, but the treatment outcome remains poor. In the literatures, the complete response rate of chemoradiotherapy in advanced esophageal cancer was about 20%, and the 2-year overall survival rate was 40%. Therefore, early detection and prediction of esophageal cancer are needed. Besides, the inconsistency of treatment effect of chemoradiotherapy may indicate some differences of esophageal cancer microenvironment among the patients. Finding out the affecting factors of microenvironment may help the decision making of treatment options and the prediction of disease prognosis. Furthermore, if we can change the affecting factors in microenvironment, we may be able to prevent the esophageal cancer formation or progression.

Esophageal tumor initiation is associated with environmental exposures, chronic inflammation, and immune cells. Several genetic and environmental factors play key roles in the formation and progression of esophageal cancer. Refluxed gastric and bile acids induce chronic inflammation and the development of intestinal metaplasia (Barrett's esophagus), which is the precursor lesion to esophageal adenocarcinoma. Toxic agent like tobacco and alcohol can cause direct esophageal injury and production of reactive oxygen species (ROS). ROS production causes direct DNA damage and tumor-initiating mutations. Besides, some literatures had reported the possible correlation with microbiota and cancer formation. Commensal bacteria (the microbiota) normally live in the gastrointestinal tract with host cell. Disruption of the relationship (dysbiosis) can influence the metabolism, tissue development, and immune response, which may cause damage to epithelial barriers, inflammation, and inducing DNA and pro-oncogenic signaling, leading to carcinogenesis in the gastrointestinal tract. The role of microbiota in the esophagus has not been widely investigated. Increasing of gram-negative bacteria increases the production of lipopolysaccharide (LPS), leading to inflammation and increased gastric reflux. The gut microbiota is associated with nutrition, the immune system, and defense of the host. It produces short chain fatty acids via anaerobic fermentation of dietary fibers in the intestine. Compared with healthy individuals, the abundance of short chain fatty acids -producing bacteria decreased and the abundance of lipopolysaccharide (LPS) -producing bacteria increased in esophageal cancer patients. Butyrate, one of the short chain fatty acids, decreases LPS-induced cytokine expression and NF-κB activation in lamina propria mononuclear cells. Esophageal microbiota theoretically plays a role in esophageal carcinogenesis.

Esophageal cancer is composed of esophageal adenocarcinoma and esophageal squamous cell carcinoma (ESCC). In esophageal adenocarcinoma, a decrease of Firmicutes, and an increase of Proteobacteria, Lactobacillus fermentum, and Tannerella forsythia have been reported. In esophageal squamous cell carcinoma, a reduction of Streptococcus species and an increase of Fusobacterium nucleatum and Porphyromonas gingivalis were observed. In Taiwan, patients with primary oropharyngeal cancer had ten times the risk of second esophageal cancer compared to the general population, and vice versa. Some specific bacteria may be associated with the co-existence of oropharyngeal cancer and esophageal cancer. However, diet is one of the most potent factors in determining microbiome integrity. Owing to the dietary difference between easterners and westerners, the dominant microbiota affecting esophageal cancer may be different. Finding out the esophageal cancer-associated specific bacteria of microbiota in Taiwan is important for further research and application for our patients.

Previously, some microorganisms could not be cultured, which would make the microbiota detection incomplete. Nowadays, 16S ribosomal RNA (16S rRNA) sequences had replaced the culture methods in detection of microbiota. In our study, we aim to compare the microbiota among healthy individuals, patients with esophageal cancer, oropharyngeal cancer, and concurrent esophageal cancer with oropharyngeal cancer in Taiwan. Through the comparison, we may find the potential risky microbiota for cancer formation or progression in Taiwan.

Investigating the Association Between Microbiota and Esophageal/Oropharyngeal Cancer

Investigating the Association, Disease Mechanism, and Clinical Application Between Microbiota and Oropharyngeal and Esophageal Cancer

We will send one patient's oral swab and esophageal mucosal tissue for screening microbiota by sequencing 16S rRNA (measured as percentage abundance per microbial species and differences in percentage abundance between the esophagus and mouth). In order to compare the similarity of microbiota between mouth and esophagus. The raw tags of data will be transformed into high-quality clean tags through the QIIME quality control process. Both alpha- and beta-diversity will be calculated with QIIME software and display with R software. We will use the Ace index to assess the richness of OTUs community and the Shannon index to assess the evenness of community diversity. Weighted UniFrac will be implemented to manifest the phylogenetic relationship of beta-diversity. To find out different genera of bacterial composition between groups, the student's t-test will be employed.

The study will compare the microbiota by sequencing 16S rRNA (measured as percentage abundance per microbial species and differences in percentage abundance between the control group and cancer group). In order to compare the difference of microbiota among esophageal cancer patients, oropharyngeal cancer patients, synchronous cancer patients, and non-cancer control. The raw tags of data will be transformed into high-quality clean tags through the QIIME quality control process. Both alpha- and beta-diversity will be calculated with QIIME software and display with R software. We will use the Ace index to assess the richness of OTUs community and the Shannon index to assess the evenness of community diversity. Weighted UniFrac will be implemented to manifest the phylogenetic relationship of beta-diversity. To find out different genera of bacterial composition between groups, the student's t-test will be employed.

National Cheng-Kung University Hospital

Neoplasm Metastasis

Neoplastic Processes

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Folic Acid

Liver Extracts

Folinic Acid

Folate

Vitamin B9

Un-resectable synchronous liver limited metastasis colorectal cancer patients undergoing neo-adjuvant chemotherapy FOLFOXIRI regimen, up to 12 cycles.

Oxaliplatin 85mg/m2 IV; Irrinotecan 165mg/m2 IV; Leucovorin 400mg/m2 IV; 5-Fluorouracil 2400mg/m2 continuous infusion in 46 hours - every 2-week cycle, up to 12 cycles.

Neo-adjuvant Chemotherapy FOLFOXIRI Regimen

Patients undergoing colorectal primary and liver resection in a single operation or staged curative procedure or no surgery

synchronous resection surgery

Hao Dinh Thy Vuong, MD

Hao Dinh Thy Vuong, M.D

This single arm study aims to evaluate the rate of conversion therapy in patients with unresectable liver-limited metastatic colorectal cancer (mCRC) using FOLFOXIRI neoadjuvant regimen and to assess the other outcome including the response rate, the survival rate and the safety profile.

Patients with liver-only metastases colorectal cancer could potentially be cured following surgical resection of metastases. Recent evidence suggest that a triplet chemotherapy regimen, FOLFOXIRI has been associated with higher R0 resection.

Eighty-nine eligible patients will be recruited at Cho Ray hospital in Vietnam. Patients will receive neoadjuvant FOLFOXIRI regimen every two weeks for up to 12 cycles and will undergo periodic imaging studies. The resectability of liver metastases will be assessed by a multidisciplinary team comprised of digestive surgeons, hepato-biliary surgeons, radiologists, and oncologists. This study will be helpful to establish a standard chemotherapy regimen for patients with liver-limited metastatic colorectal cancer. Moreover, this study will assess the surgical outcome, the response rate, the survival rate, the safety of triple drug chemotherapy and the association between conversion operable disease and various survival rate and patient's characteristics.

Surgery Outcome Treated by Neo-adjuvant Combination of Oxaliplatin, Irinotecan, Folinic Acid and Fluorouracil (FOLFOXIRI) Regimen in Synchronous Liver Limited Metastasis Colorectal Cancer

Surgery Outcome Treated by Neo-adjuvant Chemotherapy FOLFOXIRI Regimen in Colorectal Cancer With Liver-limited Synchronous Metastases

age, sex, ECOG PS, colon site, Carcinoembryonic antigen (CEA) level, RAS/ BRAF gene mutation, chemotherapy cycle numbers, Early tumor shrinkage; Depth of response; Surgery procedure; Liver lesion's number; Liver lesion's site, Liver lesion's dimension

Progression free survival (PFS) time, Overall survival (OS) time

R0 resection rate of liver metastases; Intra operative accident; Post-operative accident

Incidence of the adverse events in any grade; the serious adverse events

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Deferred Cytoreductive Nephrectomy in Synchronous Metastatic Renal Cell Carcinoma: The NORDIC-SUN-Trial	NCT03977571	Kidney Cancer Renal Cell Carc... Synchronous Neo...	Cytoreductive n... Tissue sampling	18 Years -	University of Aarhus
The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial	NCT05753839	Kidney Cancer Clear Cell Rena... Synchronous Neo...	Cytoreductive n... Cytoreductive n... Human-derived m...	18 Years -	Yonsei University
The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma in Immuno-oncology Era: SEVURO-CN Trial	NCT05753839	Kidney Cancer Clear Cell Rena... Synchronous Neo...	Cytoreductive n... Cytoreductive n... Human-derived m...	18 Years -	Yonsei University
Investigating the Association Between Microbiota and Esophageal/Oropharyngeal Cancer	NCT05412628	Microbial Colon... Esophageal Canc... Oropharyngeal N... Synchronous Neo...	Oral swab test	20 Years - 99 Years	National Cheng-Kung University Hospital
Investigating the Association Between Microbiota and Esophageal/Oropharyngeal Cancer	NCT05412628	Microbial Colon... Esophageal Canc... Oropharyngeal N... Synchronous Neo...	Oral swab test	20 Years - 99 Years	National Cheng-Kung University Hospital
Surgery Outcome Treated by Neo-adjuvant Combination of Oxaliplatin, Irinotecan, Folinic Acid and Fluorouracil (FOLFOXIRI) Regimen in Synchronous Liver Limited Metastasis Colorectal Cancer	NCT05362825	Liver Metastasi... Synchronous Neo...	Neo-adjuvant Ch... synchronous res...	18 Years - 75 Years	Cho Ray Hospital
Surgery Outcome Treated by Neo-adjuvant Combination of Oxaliplatin, Irinotecan, Folinic Acid and Fluorouracil (FOLFOXIRI) Regimen in Synchronous Liver Limited Metastasis Colorectal Cancer	NCT05362825	Liver Metastasi... Synchronous Neo...	Neo-adjuvant Ch... synchronous res...	18 Years - 75 Years	Cho Ray Hospital

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