Washed Microbiota Transplantation for The Treatment of Oncotherapy-Related Intestinal Complications

Cancer Clinical Trial

Official title:

Efficacy and Safety of Washed Microbiota Transplantation for The Treatment of Oncotherapy-Related Intestinal Complications

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04721041
• Other study ID #: Cancer-CN-202010
• Status: Recruiting
• Phase: N/A
• Start date: January 26, 2021
• Est. completion date: May 2025

Study information

• Verified date: March 2024
• Source: The Second Hospital of Nanjing Medical University
• Contact: Faming Zhang, MD,PHD
• Phone: 086-25-58509883
• Email: fzhang[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gut microbiota, known as "unrecognized organs", is closely related to the occurrence and development of tumors. Cancer is thought to occur secondary to local chronic inflammation. And some bacteria, such as Helicobacter pylori, also have direct genotoxicity, changing intracellular signaling pathways and thus causing abnormal cell growth. Systemic intestinal dysbiosis may lead to cancer, and fecal microbiota transplantation (FMT) can be a new weapon in anti-cancer treatment.Washed microbiota transplantation (WMT), a new stage of FMT, is based on the automatic microfiltration machine (GenFMTer, Nanjing, China) and the following repeated centrifugation plus suspension with support from specific facilities. The investigators conducted a prospective, one-arm, open-label study on the efficacy and safety of WMT in the treatment of oncotherapy-related complications. This study aimed to exploring the therapeutic potential of WMT in the treatment of oncotherapy-related intestinal complications and improving the quality of life of patients.

Description:

Gut microbiota, known as "unrecognized organs", is closely related to the occurrence and development of tumors. Cancer is thought to occur secondary to local chronic inflammation. And some bacteria, such as Helicobacter pylori, also have direct genotoxicity, changing intracellular signaling pathways and thus causing abnormal cell growth. Systemic intestinal dysbiosis may lead to cancer, and fecal microbiota transplantation (FMT) can be a new weapon in anti-cancer treatment. The reduction of intestinal flora diversity may lead to intestinal dysbiosis, thereby reducing the body immunity and promoting the formation and development of neoplasm. It has been reported that FMT can be used to treat melanoma, liver cancer and prostate cancer after immunotherapy failed. But the mechanism of gut microbiota on the tumor itself remains to be further explored. In 2019, an Italian study reports the efficacy of FMT for diarrhea induced by tyrosine kinase inhibitors in the treatment of renal cell carcinoma, suggesting the therapeutic potential of gut microbiota for tumor-related gastrointestinal complications [1].

Fecal Microbiota transplantation (FMT), the most classic way to treat diseases using gut microbiota [2], refers to the transplantation of functional microbiota in the feces of healthy people into the intestines of patients. It can reconstruct the overall gut microbiota of patients, thus treating gastrointestinal diseases and external gastrointestinal diseases of patients. In 2013, FMT was for the first time coined into the treatment guidelines on recurrent CDI, and now it plays an important role as a key treatment for clostridium difficile infection [3]. Washed microbiota transplantation (WMT), a new stage of FMT, is based on the automatic microfiltration machine (GenFMTer, Nanjing, China) and the following repeated centrifugation plus suspension with support from specific facilities. Compared with manual FMT, WMT can reduce the rate of adverse events (such as fever, diarrhea, abdominal pain, abdominal distension, nausea and vomiting, etc.) without affecting the efficacy. In addition, Zhang et al. have proved that WMT is better than the manual preparation of FMT in improving safety, enriching the precise amount of microbiota and quality controllable in practice [4]. In December 2019, A panel of 28 experts from 22 hospitals or institutes in 15 cities has contributed to the "Nanjing consensus on methodology of washed microbiota transplantation" according to the international standards, and the consensus is published in Chinese Medical Journal in July 2020 [5].

Therefore, the investigators conducted a prospective, one-arm, open-label study on the efficacy and safety of WMT in the treatment of oncotherapy-related intestinal complications. This study aimed to exploring the therapeutic potential of WMT in the treatment of oncotherapy-related intestinal complications and improving the quality of life of patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Age =18 years old; 2. Diagnosed as malignant tumor; 3. Patients who underwent cancer-related treatment suffering from gastrointestinal symptoms(e.g., abdominal pain, diarrhea, abdominal distension, and difficulty defecating) occurred after standard tumor therapy (such as chemotherapy, radiation, immunotherapy, surgical treatment, etc.); 4. Estimated time of survival = 3 months, and vital signs were stable); 5. Physically qualified and intended to undergo FMT;

Exclusion Criteria:

• 1. Patients who were pregnant or nursing; 2. Patients who were unable or unwilling to undergo a gastroscopy or colonoscopy; 3. Patients with cardiopulmonary failure; 4. Antibiotics, PPI, probiotics, and other drugs that alter gut microbiota were used in the previous week; 5. history of inflammatory bowel disease and intestinal symptoms unrelated to tumor treatment; 6.Serious uncontrolled diseases and acute infectious diseases;

Related Conditions & MeSH terms

• Cancer
• Intestinal Complications

Intervention

Procedure:
• Washed Microbiota Transplantation (WMT)
Washed microbiota suspension (5u) delivered through nasogastric tube, nasojejunal tube or oral. Dose and frequency: 5u, three times.

Locations

Country	Name	City	State
China	Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The Second Hospital of Nanjing Medical University

Country where clinical trial is conducted

China, 

References & Publications (3)

Prisciandaro M, Ratta R, Massari F, Fornarini G, Caponnetto S, Iacovelli R, De Giorgi U, Facchini G, Scagliarini S, Sabbatini R, Caserta C, Peverelli G, Mennitto A, Verzoni E, Procopio G. Safety and Efficacy of Cabozantinib for Metastatic Nonclear Renal Cell Carcinoma: Real-world Data From an Italian Managed Access Program. Am J Clin Oncol. 2019 Jan;42(1):42-45. doi: 10.1097/COC.0000000000000478. Erratum In: Am J Clin Oncol. 2019 Apr;42(4):412. — View Citation

Surawicz CM, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol. 2013 Apr;108(4):478-98; quiz 499. doi: 10.1038/ajg.2013.4. Epub 2013 Feb 26. — View Citation

Zhang T, Lu G, Zhao Z, Liu Y, Shen Q, Li P, Chen Y, Yin H, Wang H, Marcella C, Cui B, Cheng L, Ji G, Zhang F. Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening. Protein Cell. 2020 Apr;11(4):251-266. doi: 10.1007/s13238-019-00684-8. Epub 2020 Jan 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Scores of gastrointestinal symptoms	Gastrointestinal symptoms will be evaluated according to NCI-CTC 5.0	8 weeks
Primary	Stool frequency and consistency	Stool frequency and consistency will be evaluated according to The Bristol Stool Form Scale (BSFS).	8 weeks
Secondary	Adverse events	New onset of symptoms and the exacerbation of previous symptoms were recorded as adverse events (AEs)	1 year
Secondary	Karnofsky Performance Status (KPS) scale	Changes in functional status of patients will be assessed according to the Karnofsky Performance Status (KPS) scale (ranging from 0 [dead] to 100 [normal activity, no evidence of disease])	8 weeks