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

Launched by UNIVERSITY OF MINNESOTA · Feb 4, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called Restorative Microbiota Therapy (RMT) for patients who have developed colitis, or inflammation of the colon, due to immune checkpoint inhibitors (ICIs), which are medications used to treat certain cancers. When patients experience severe colitis that does not improve with standard steroid treatments, there is a need for alternative therapies. This study aims to assess whether RMT can be a safe and effective option for these patients.

To participate in the trial, individuals must have advanced cancer and have received at least two doses of ICIs within the past six months. They should also be experiencing ongoing diarrhea that hasn’t responded to steroids, and they must have healthy organ function. Participants will receive either the RMT treatment or a placebo, and their health will be closely monitored throughout the study. It’s important to note that the trial is not yet recruiting participants, and those interested will need to meet specific criteria to qualify. This research could help find new treatment options for patients suffering from this challenging condition.

Gender

ALL

Eligibility criteria

• 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 TNFα 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