Probiotics Preventing Immune Checkpoint Inhibitor-Induced Colitis

Overview

About this study

This is a prospective, pilot, single arm study to evaluate the incidence of IIC in patients with solid malignancies receiving VSL#3 and ICIs. Given the fact that the effects of over-the-counter probiotics in reducing the risks of IIC remains largely unknown. Given that this is a small pilot study to generate preliminary data, there will be no randomization in this trial. The results of this trial will provide a foundation for the future development of larger definitive randomized controlled trials. Patients with solid malignancy who will be receiving ICI as per standard of care will be enrolled in this trial.  Patients will receive VSL#3® 450B sachets probiotics, which will be provided as part of this trial, at least 3 days but preferably 1-2 weeks prior to starting on ICIs. Patients will be followed per standard of care during ICI treatment and continue VSL#3 for 12 more weeks while on ICI. Patients will complete dietary questionnaire and have research blood draws and stool collections at baseline prior to starting VSL#3 and 3 additional time points. Adherence to the probiotic schedule will be captured in a study diary.  Adverse events as well as incidence and severity of IIC will be graded using NCI CTCAE version 5. Patients will have imaging performed per standard of care.

Primary Goal

  • To evaluate the incidence of immune checkpoint inhibitors (ICI)-induced colitis (IIC) in patients with solid malignancies receiving over-the-counter multi-strain probiotic blend and ICIs in both cohorts: (1) anti-CTLA-4 +/- anti-PD-1/PD-L1, and (2) anti-PD-1/PD-L1 +/- chemo.  

Secondary Goals

  • To evaluate the safety of multi-strain probiotic blend in cancer patients receiving ICIs.
  • To evaluate the clinical outcomes related to IIC, including the incidence of IIC, hospitalization, treatment delays, and administration of immunosuppressants.

Exploratory Goals

  • To evaluate changes in gut microbiome with ICIs and multi-strain probiotic blend.
  • To evaluate changes in immune response with ICIs and multi-strain probiotic blend.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria

  1. Male or female age ≥ 18 years.
  2. Eastern Cooperative Oncology Group (ECOG) performance status ≤
  3. Histologically confirmed advanced solid malignancy.
  4. Will be starting on ICIs.
  • For cohort 1: Ipilimumab with or without anti-PD-1/PD-L1 including but not limited to pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, or durvalumab.
  • For cohort 2: Anti-PD-1/PD-L1 described above with or without chemotherapy.
  1. Patients must have adequate organ and marrow function as defined below:
  • Absolute neutrophil count (ANC) ≥ 1000/mm3
  • Platelet count ≥ 75,000/mm3
  • Hemoglobin ≥ 9.0 g/dL
  • Creatinine ≤ 2 x ULN
  • SGOT (AST) ≤ 2 x ULN
  • Albumin ≥ 3 g/dL
  1. Willing and able to provide research stool and blood samples.
  2. Negative serum pregnancy test done ≤ 7 days prior to enrollment, for women of childbearing potential only.
  3. Capable of providing valid informed consent.
  4. Willing to return to enrolling institution for all study visits (blood draws, etc).

Exclusion Criteria 

  1. Requires prolonged systemic antibiotic therapy for other condition and recent systemic antibiotic within the past 2 weeks
  2. Fecal microbiota transplant (FMT) within the past 6 months
  3. FMT with an associated serious adverse event related to the FMT product or procedure.
  4. Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of over-the-counter probiotics.
  5. Immunocompromised patients including patients known to be HIV positive or those on chronic steroids > 20 mg prednisone a day or prednisone-equivalent. Note: Must be off systemic steroids at least 90 days prior to enrollment. However, topical steroids, inhalants or steroid eye drops are permitted.
  6. History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn’s disease, or microscopic colitis.
  7. History of chronic diarrhea.
  8. History of celiac disease.
  9. Currently has a colostomy.
  10. Intraabdominal surgery related to gastrointestinal tract within the last 60 days.
  11. Evidence of active, severe colitis.
  12. History of short gut syndrome or motility disorders.
  13. Requires the regular use of medications to manage bowel hypermotility.
  14. Active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to randomization. Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves’ disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Saranya Chumsri, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available