Lactulose to Improve Gut Health in Cancer Patients Receiving Immunotherapy
ConditionCancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Chicago
About this trial
The purpose of this study is to see if lactulose can improve the effectiveness of immunotherapy in patients with advanced cancer.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Inclusion Criteria Phase I
Patients must have a histologically confirmed malignancy that is to receive exclusively ICIs (no chemotherapy or RT in combination) per standard of care during the time in which lactulose will be administered. This includes, but is not limited to, melanoma, cutaneous squamous cell carcinoma, non-small cell lung cancer, mesothelioma, head and neck squamous cell carcinoma, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial cancer, MSI/MMRd cancer, cancers with high tumor mutational burden (>=10 muts/mB), esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma. Anti-PD-1 or anti-PD-L-1 therapy combinations with anti-LAG-3 or anti-CTLA-4 combinations are permitted.
Age ≥18 years. Because no dosing or adverse event data are currently available on the use of lactulose in combination with ICIs in patients <18 years of age, children are excluded from this study.
ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
Disqualifiers
Exclusion Criteria for Phase I
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ICIs or lactulose.
Current serious concomitant illnesses include cardiovascular diseases (such as uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmias), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders, including HIV or AIDS-related illnesses or active hepatitis B or C virus.
The ongoing use of systemic antibiotics or the previous use of antibiotics in the 2 weeks before enrollment.
Trial design
Design model
Sequential
Treatments tested in this trial
Lactulose
DrugLactulose 10 g daily with standard-of-care Immune checkpoint inhibitors (ICIs).
Treatment groups
55 Participants
are divided into 2 treatment groupsGroup A: Phase 1 ArmExperimental treatment 1 intervention
Group B: Phase 2 ArmExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Phase 1-
Change in Bifidobacterium abundance in stool from baseline to week 3.
Time frame
Baseline to week 32
Overall Response Rate
Assessment of cancer response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame
Through study completion, an average of 2 yearsSecondary outcomes
1
Phase 1-Safety and tolerability
Incidence and severity of adverse events (Common Terminology Criteria for Adverse Events (CTCAE) v5.0) and dose limiting toxicities.
Time frame
3 weeks2
Phase 1- Effects of lactulose
Change from baseline to week 3 in stool and blood metabolite profiles.
Time frame
Baseline to week 33
Phase 1- Effects of lactulose
Change from baseline to week 3 in the abundance of secondary gut microbial taxa and change in alpha diversity indices from baseline to week 3.
Time frame
Baseline to week 34
Phase 1- Anti-Tumor Evalution
Evaluating the duration of response, disease control, overall survival, progression free survival and best Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response.
Time frame
Baseline to week 3Sponsors and contacts
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Source ClinicalTrials.gov