GLP-1 RA Plus SOC Treatment in First-line, Metastatic Pancreatic, Colorectal, or Hepatocellular Cancer
Trial statusRecruiting
Trial phaseEarly Phase 1
Trial typeInterventional
Biological sexAll
Age18-99
SponsorUniversity of Arizona
About this trial
There is a growing number of patients diagnosed with gastrointestinal cancers who are also simultaneously being treated with GLP-1 Receptor Agonists (RA)s. To date, no clinical trial data exists to establish safety and/or feasibility with use of GLP-1 RAs during chemotherapy in the metastatic setting. The goal of this clinical trial is to evaluate the safety, tolerability, preliminary efficacy, and correlative analyses of combining GLP-1 RAs with standard chemotherapy in patients with metastatic pancreatic, colorectal, or hepatocellular cancers in the first-line setting.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histological or cytological diagnosis of pancreatic adenocarcinoma or colorectal adenocarcinoma. Previous tumor tissue testing is acceptable. Please refer to the "additional HCC cohort criteria" below.
The subject has disease that is not amenable to curative-intent management (e.g., oligometastatic disease)
Measurable disease per RECIST v1.1 as determined by the investigator
Patients must be appropriate candidates for first-line, SOC treatment.
Disqualifiers
The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) for metastatic and/or unresectable disease.
BMI < 25 kg/m2
For colorectal cancer only - Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) tumors.
For colorectal cancer only - BRAF V600E mutant tumors.
Trial design
Design model
Parallel
Treatments tested in this trial
GLP1-RA (semaglutide)
DrugPatients will receive 6 months of weekly semaglutide; weekly subcutaneous injection; dose escalation will occur every 4 weeks with dose titration as follows: 0.25 mg → 0.5 mg → 1 mg → 1.7 mg → Maintenance at 2.4 mg or 1.7 mg pending tolerability.
Treatment groups
30 Participants
are divided into 3 treatment groupsGroup A: Metastatic Pancreatic Adenocarcinoma (PDAC)Experimental treatment 1 intervention
Group B: Metastatic Colorectal Adenocarcinoma (CRC)Experimental treatment 1 intervention
Group C: Metastatic Hepatocellular Carcinoma (HCC)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of Treatment Emergent Adverse Events [Safety] attributed to GLP1-RA and/or its interaction with chemotherapy
Safety is defined as the incidence of grade ≥3 adverse events (AEs) as defined by CTCAE v5.0, attributed to GLP-1 RA and/or its interaction with chemotherapy
Time frame
Up to 6 months or at time of disease progression, whichever comes firstSecondary outcomes
1
Proportion of patients who complete planned chemotherapy with concurrent GLP-1 RA without Dose Modifications or Early Termination [Tolerability]
Endpoints for this outcome include: proportion of patients who complete planned chemotherapy with concurrent GLP-1 RA without unplanned dose reductions or delays \> 14 days; dose modifications; early termination: rate of early study withdrawal or discontinuation due to treatment-related adverse effects.
Time frame
Up to 6 months or at time of disease progression, whichever comes first2
Overall Response Rate [Efficacy]
Overall response rate (ORR) will be measured using the radiographic objective Response Rate as defined by RECIST v1.1
Time frame
Up to 6 months or at time of disease progression, whichever comes first3
Progression Free Survival [Efficacy]
Progression free survival (PFS) is defined as the duration on treatment until progression as measured from start of treatment until disease progression or death from any cause. We will use 95% CI for PFS on those patients deemed efficacy eligible.
Time frame
Up to 6 months or at time of disease progression, whichever comes firstOther outcomes
1
Evaluate changes in serologic markers of inflammation and metabolism (Fasting glucose).
Changes in serologic markers of inflammation and metabolism will be measured by looking at multiple labs that measure Glycemic control and Insulin resistance as well as Inflammatory and Metabolic biomarkers. Fasting glucose is a measure of blood sugar when it should be at its lowest. Changes will be presented via repeated measures, ANOVA, or mixed-effects modeling.
Time frame
Up to 6 months or at time of disease progression, whichever comes first2
Evaluate changes in serologic markers of inflammation and metabolism (HbA1c).
Changes in serologic markers of inflammation and metabolism will be measured by looking at multiple labs that measure Glycemic control and Insulin resistance as well as Inflammatory and Metabolic biomarkers. HbA1c is a lab that measures average blood sugar levels over 2-3 months. Changes will be presented via repeated measures, ANOVA, or mixed-effects modeling.
Time frame
Up to 6 months or at time of disease progression, whichever comes first3
Evaluate changes in serologic markers of inflammation and metabolism (HOMA-IR).
Changes in serologic markers of inflammation and metabolism will be measured by looking at multiple labs that measure Glycemic control and Insulin resistance as well as Inflammatory and Metabolic biomarkers. HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) is a mathematical score used to measure insulin resistance. Changes will be presented via repeated measures, ANOVA, or mixed-effects modeling.
Time frame
Up to 6 months or at time of disease progression, whichever comes first4
Evaluate changes in serologic markers of inflammation and metabolism (CRP).
Changes in serologic markers of inflammation and metabolism will be measured by looking at multiple labs that measure Glycemic control and Insulin resistance as well as Inflammatory and Metabolic biomarkers. CRP (C-Reactive Protein) is a lab used to test for inflammation. Changes will be presented via repeated measures, ANOVA, or mixed-effects modeling.
Time frame
Up to 6 months or at time of disease progression, whichever comes firstSponsors and contacts
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Source ClinicalTrials.gov