A Pilot Study Testing the Safety and Feasibility of Restorative Microbiota Therapy (RMT) in Patients With Refractory Immune-checkpoint Inhibitor-related Colitis

Colitis Clinical Trial

Official title:

A Pilot Study Testing the Safety and Feasibility of Restorative Microbiota Therapy (RMT) in Patients With Refractory Immune-checkpoint Inhibitor-related Colitis

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05726396
• Other study ID #: MNCCTN025
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2024
• Est. completion date: December 1, 2024

Study information

• Verified date: January 2024
• Source: University of Minnesota
• Contact: Amit Kulkarni, MBBS
• Phone: 612-301-8581
• Email: kulkarni[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Immune-related colitis from immune checkpoint inhibitors (ICI) is a common adverse effect causing significant morbidity and impairment of quality of life (QoL). Steroids are the first line of treatment for severe ICI induced Immune- mediated diarrhea and colitis (IMDC). If there is no improvement in 48 to 72 hours, other immunosuppressive agents (infliximab, vedolizumab) are recommended. However, efficacy data supporting the use of immunosuppressives for steroid refractory IMDC is limited by case reports/series. Clinical trials focusing on steroid-refractory colitis are sparse. Novel treatments for IMDC outside of blanket immunosuppression are needed. There is robust evidence to suggest that gut microbial diversity and composition is associated with both ICI efficacy and toxicity. Preliminary studies have shown that pathophysiology of immune mediated colitis may be related to loss of gut microbial diversity. Recently, multiple case series have shown the utility of fecal microbiota transplant for treatment of refractory IMDC providing the proof of concept. This is a pilot randomized placebo controlled study to assess the safety and feasibility of oral restorative microbiota therapy (RMT) in patients with steroid- refractory IMDC.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Advanced or metastatic solid tumors who have received at least two doses of ICI (PD-1/PD-L1 with or without CTLA-4 inhibitor) within 6 months of the onset of steroid-refractory IMDC symptoms. The ICI may be used as a single agent, or combination or ICI in combination with other cytotoxic chemotherapy or targeted therapy for curative or palliative intent treatment.

• Meet one of the criteria for steroid refractory IMDC defined as:

Persistent symptoms (NCI CTCAE v 5.0 Grade = 2 diarrhea) 72 hours after the patient received the high-dose corticosteroid therapy (>1 mg/kg/d prednisone or equivalent) or Symptoms relapsed (NCI CTCAE v 5.0 Grade = 2 diarrhea) upon tapering to 1mg/kg/d or more of prednisone or equivalent or Persistent symptoms (ongoing Grade = 2 diarrhea per CTCAE v5.0.) following use of a one or more biologic agent (i.e. either a TNFa inhibitor or an anti-integrin) in addition to steroids.

• Adequate organ function within 14 days of study enrollment defined as: Hematology:

Hemoglobin =9.0 g/dL, absolute neutrophil count (ANC)

=1,000/mcL, platelets =75,000/mcL, Hepatic function: Total bilirubin = 1.5x upper limit of normal (ULN), AST (SGOT) and ALT (SGPT) = 2.5 x institutional ULN unless liver metastases are present, in which case it must be =5x ULN) Renal function: measured creatinine clearance >40 mL/min or estimated glomerular filtration rate (eGFR) > 40 mL/min If AST/ALT and serum creatinine elevation are suspected to be irAEs, patients are eligible as long as the irAE are controlled (i.e. not getting worse at the time of enrollment)

• Able to provide written consent prior to any research related activities

Exclusion Criteria:

• Known current pregnancy or breastfeeding

• Diagnosis of concomitant infectious colitis (e.g. C. difficile or other bacterial or viral source or parasitic), unless the patient has finished an appropriate length of treatment with antibiotics as indicated for each diagnosis at the time of enrollment

• Receiving another investigational agent or has received an investigational agent within 60 days of study enrollment

• Any other uncontrolled Grade = 3 infection at the time of enrollment (Concomitant systemic antibiotics for non-GI infections are allowed)

• Active documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

• Previous documented history of chronic diarrhea from non-IMDC causes

• CTCAE v 5 Dysphagia Grade 2 (symptomatic and altered eating/swallowing) or greater

• Known risk of aspiration based on history or current complaints

Related Conditions & MeSH terms

• Colitis

Intervention

Drug:
• RMT
A single loading dose of RMT capsules containing ~5 x 10 11 bacteria on day 1 followed by 2 x 10 11 bacteria daily for 6 days. The RMT capsule preparation (~2-5 capsules, size 00) is self-administered on an empty stomach with at least one glass of water. Clear liquids are allowed, and food can be resumed 2 hours after administration.
• Placebo
Participants will receive an identical looking placebo capsules daily for 7 days (i.e 5 placebo capsules on day 1), followed by 2 placebo capsules daily from Day 2-7. The placebo capsule preparation is self-administered on an empty stomach with at least one glass of water. Clear liquids are allowed, and food can be resumed 2 hours after administration.

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	occurrence of adverse events	assessed by the occurrence of adverse events Grade =3 per NCI's Common Terminology Criteria for Adverse Events (CTCAE v5.0).	6 months after baseline
Secondary	Primary efficacy of oral RMT in inducing clinical remission- Day 10	diarrhea of Grade <= 1 of refractory IMDC at Day 10 (+-3) from the 1st dose of RMT	Day 10
Secondary	Primary efficacy of oral RMT in inducing clinical remission- Day 30	diarrhea of Grade <= 1 of refractory IMDC at Day 30 (+-5) from the 1st dose of RMT	Day 10
Secondary	Days for clinical remission	Efficacy of RMT to induce a clinical remission of refractory IMDC as measured by time in days necessary to achieve a diarrhea of Grade <=1	Day 180