Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Rare Diseases

Nasopharyngeal Carcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Anti-Infective Agents

All Drugs and Chemicals

Anti-Bacterial Agents

Antibiotics, Antitubercular

The patients (1) were diagnosed with NPC; 2)18\< Age \<75.

(1) 18\< Age \<75, and Han Chinese residents living in Hunan more than 3 years. (2) Health examination population who physical examination, assistant examination and serological examination were normal; None of the patients had rhinitis or used any antibiotics during the three months last 3 months.

This study investigated the correlation between the changes in the intestinal flora and NPC by an examination of the intestinal flora and multiple clinical indicators of the blood of 8 carefully screened patients of familial NPC, 24 patients of sporadic NPC and 27 healthy controls and a comparison of the differences in their intestinal flora structures and biological functions. By analyzing the function of the intestinal floras of NPC patients, we aimed to provide a better biological marker for patients with familial and sporadic NPC and constructed a disease prediction model for high-risk populations.

Nasopharyngeal carcinoma (NPC) is a malignant nasopharyngeal disease with a complicated etiology that occurs mostly in southern China. Intestinal flora imbalance is believed to be associated with a variety of organ malignancies. Currently, the relationship between intestinal flora and NPC is not clear, although many studies have shown that intestinal flora can be used as a biomarker for many cancers and to predict cancer.

To compare the differences in intestinal flora compositions and biological functions among patients with familial NPC (NPC_F), patients with sporadic NPC (NPC_S) and healthy controls (NOR), we compared the intestinal flora DNA sequencing and hematological testing results between every two groups using bioinformatic methods.

The faeces and the sera of the recruited participants

Intestinal Flora Sequencing for Nasopharyngeal Carcinoma

Intestinal Flora Disruption and a Novel Intestinal Biomarker Associated With Nasopharyngeal Carcinoma

NPC patients with a first degree NPC family history

NPC patients without any tumor family history

The Third Xiangya Hospital of Central South University

Vancomycin

Antibodies

Immunoglobulins

5 times dose of RX-af01 in combination with toripalimab

Mixed bacteria in combination with toripalimab

Pretreatment： vancomycin: 125mg po, tid, D-6 to D-3 RX-af01: 2 capsules, bid, po, D-2 to D0 Treatment (Every 3 weeks) RX-af01: 1 capsule, bid, po, every day Toripalimab: 240mg, ivdrip, D1, every 3 weeks.

RX-af01

Pretreatment： vancomycin: 125mg po, tid, D-5 to D-3

Mixed bacteria

High dose RX-af01

Miao-Zhen Qiu

Shuang-Zhen Chen

Miao-zhen Qiu, MD

Rui-hua Xu, MD, PhD

This phase I trial evaluates the effects of RX-af01 in combination with toripalimab (PD-1 antibody), in treating patients with refractory advanced solid tumors, including melanoma, nasopharyngeal squamous carcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, renal cell carcinoma, et al. RX-af01 is a kind of anti-tumor intestinal bacteria developed by our research group. Its main components are symbiotic bacteria from human intestine - Alisipes finegoldii (A. finegoldii.), which is a Gram negative anaerobic bacteria. Our previous research shows that A finegoldii. can significantly enhance the anti-tumor activity of PD-1 antibody in multiple mouse tumor models. Mechanism research shows that A finegoldii. can increase the infiltration of CD4 and CD8 positive immune cells in the tumor microenvironment, and enhances the anti-tumor activity of immune cells. The primary aim of this study is to explore the efficacy and safety of RX-af01 combined with PD-1 antibody in refractory advanced solid tumors.

This is a phase Ib study to evaluate the effects of RX-af01 in combination with toripalimab (PD-1 antibody), in treating patients with refractory advanced solid tumors, including melanoma, nasopharyngeal squamous carcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, renal cell carcinoma, et al. This study will include 3 chorts. Cohort 1 uses the regular dose of RX-af01. Cohort 2 uses a high dose of RX-af01 which is 5 times of the regular dose of RX-af01. Cohort 3 uses a mixed bacteria including RX-af01, Bifidobacterium longum RX02 and Ligilactobacillus salivarius RX02.

Primary endpoint:

To determine the safety and efficacy of bacterial strain RX-af01 in combination with toripalimab in refractory advanced solid tumors.

Secondary endpoint:

1. Progression free survival (PFS)
2. Overall survival (OS)
3. Duration of response (DOR)
4. Tumor microenvironment
5. Changes in flora species/abundance

Safety and Efficacy of RX-af01 Combined With PD-1 Antibody

Safety and Efficacy of Bacterial Strain RX-af01 Combined With PD-1 Antibody in Patients With Refractory Advanced Solid Tumors

Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, including complete response (CR) and partial response (PR).

From the time of enrollment to the date of death or last followup.

From the time of enrollment to the date of disease progression or death or last followup.

The time from the first assessment of CR or PR to the first assessment of PD or death (caused by any reason)

Infiltration of immune cells, including CD8+T cell, Treg cell et al.

Using translational methods, will compute the Shannon index at baseline for a comparison of microbial diversity.

Sun Yat-sen University

Professor

Digestive System Diseases

Carcinoma, Squamous Cell

Esophageal Squamous Cell Carcinoma

Neoplasms, Squamous Cell

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

Immunomodulating Agents

Sintilimab and chemotherapy are carried out at the same time for every 3 weeks

SintilimabCombined With Chemotherapy

Jun Zhao

This study collects stool, blood, and tumor tissue samples from patients with locally advanced esophageal cancer after receiving Sintilimab and chemotherapy to explore the efficacy and intestinal microbes of chemotherapy combined with neoadjuvant immunotherapy for locally advanced operable thoracic esophageal squamous cell carcinoma The main purpose is the relationship between its metabolites, and it will also explore the changes of intestinal flora diversity and metabolites before and after esophageal squamous cell carcinoma chemotherapy combined with immune neoadjuvant therapy

Correlation Between the Efficacy of Neoadjuvant Chemotherapy Combined With Immunotherapy of Operable Thoracic Esophageal Squamous Cell Carcinoma and the Metabolites of Intestinal Flora

Alpha-diversity of samples, that measures both the richness and diversity of species within a group, was calculated on taxa that were observed at least once.

Beta-diversity, that measures the differences in microbiome composition between groups.

Discovery of gut microbes and metabolic markers that can predict the efficacy of chemotherapy combined with neoadjuvant immunotherapy for esophageal squamous cell carcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intestinal Flora Sequencing for Nasopharyngeal Carcinoma	NCT04094545	Nasopharyngeal ...		18 Years - 75 Years	The Third Xiangya Hospital of Central South University
Safety and Efficacy of RX-af01 Combined With PD-1 Antibody	NCT05576961	Solid Tumor Immune Checkpoi... Intestinal Flor...	RX-af01 Mixed bacteria High dose RX-af...	18 Years -	Sun Yat-sen University
Correlation Between the Efficacy of Neoadjuvant Chemotherapy Combined With Immunotherapy of Operable Thoracic Esophageal Squamous Cell Carcinoma and the Metabolites of Intestinal Flora	NCT05199649	Esophageal Squa... Intestinal Flor...	SintilimabCombi...	18 Years - 75 Years	The First Affiliated Hospital of Soochow University
Correlation Between the Efficacy of Neoadjuvant Chemotherapy Combined With Immunotherapy of Operable Thoracic Esophageal Squamous Cell Carcinoma and the Metabolites of Intestinal Flora	NCT05199649	Esophageal Squa... Intestinal Flor...	SintilimabCombi...	18 Years - 75 Years	The First Affiliated Hospital of Soochow University
Safety and Efficacy of RX-af01 Combined With PD-1 Antibody	NCT05576961	Solid Tumor Immune Checkpoi... Intestinal Flor...	RX-af01 Mixed bacteria High dose RX-af...	18 Years -	Sun Yat-sen University

Spots Global Cancer Trial Database for intestinal flora