Cancer
Conditions
Brief summary
The purpose of this study is to see if lactulose can improve the effectiveness of immunotherapy in patients with advanced cancer.
Interventions
DRUGLactulose
Lactulose 10 g daily with standard-of-care Immune checkpoint inhibitors (ICIs).
Sponsors
University of Chicago
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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). * Patients must be able to ingest liquids. * Inclusion Criteria Phase II * Patients must have a histologically confirmed cutaneous or mucosal melanoma. Uveal melanoma is excluded. * Measurable disease per RECIST 1.1.32 * Documented primary or acquired resistance to anti-PD-1 and anti-CTLA4 therapy per SITC guidelines.21 Primary resistance is defined as disease progression after a minimum of 6 weeks of therapy, provided the patient has received at least two full cycles of treatment, and there has been no prior evidence of clinical benefit (partial response, complete response, or stable disease lasting at least 6 months). Acquired resistance is defined as disease progression after an initial clinical benefit while still on therapy or within 12 weeks of discontinuing therapy, provided the patient received at least two cycles and 6 weeks of therapy. * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. * Planned to receive standard ICI therapy (no RT/ICI or chemotherapy/ICI combinations). * 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). * Patients must be able to ingest liquids.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1- | Baseline to week 3 | Change in Bifidobacterium abundance in stool from baseline to week 3. |
| Overall Response Rate | Through study completion, an average of 2 years | Assessment of cancer response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1-Safety and tolerability | 3 weeks | Incidence and severity of adverse events (Common Terminology Criteria for Adverse Events (CTCAE) v5.0) and dose limiting toxicities. |
| Phase 1- Effects of lactulose | Baseline to week 3 | Change from baseline to week 3 in stool and blood metabolite profiles. |
| Phase 1- Anti-Tumor Evalution | Baseline to week 3 | Evaluating the duration of response, disease control, overall survival, progression free survival and best Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response. |
| Phase 2- Safety and tolerability | 12 weeks | Incidence and severity of adverse events (Common Terminology Criteria for Adverse Events (CTCAE) v5.0) and dose limiting toxicities. |
| Phase 2- Evaluate changes of stool and serum | Baseline to week 12 | Change from baseline to week 3 in stool and blood metabolite profiles. |
| Phase 2- Secondary Gut Evaluation | Baseline to week 3 | Change from baseline to week 3 in the abundance of gut microbial tax. |
| Phase 2- Gut Evaluation | Baseline to week 12 | Change in alpha diversity indices from baseline to week 12. |
Countries
United States
Contacts
CONTACTClinical Trials Intake Intake
PRINCIPAL_INVESTIGATORDaniel Olson
University of Chicago
Outcome results
None listed