GLP-1 RA Plus SOC Treatment in First-line, Metastatic Pancreatic, Colorectal, or Hepatocellular Cancer

NCT07627191 | Not Yet Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00007884
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer; Hepatocellular Carcinoma; Pancreatic Cancer

Keywords

GLP1 receptor agonists; gastrointestinal cancer

Outcome Measures

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

  Up to 6 months or at time of disease progression, whichever comes first

Secondary Outcomes (3)

• Proportion of patients who complete planned chemotherapy with concurrent GLP-1 RA without Dose Modifications or Early Termination [Tolerability]

  Up to 6 months or at time of disease progression, whichever comes first

• Overall Response Rate [Efficacy]

  Up to 6 months or at time of disease progression, whichever comes first

• Progression Free Survival [Efficacy]

  Up to 6 months or at time of disease progression, whichever comes first

Other Outcomes (13)

• Evaluate changes in serologic markers of inflammation and metabolism (Fasting glucose).

  Up to 6 months or at time of disease progression, whichever comes first

• Evaluate changes in serologic markers of inflammation and metabolism (HbA1c).

  Up to 6 months or at time of disease progression, whichever comes first

• Evaluate changes in serologic markers of inflammation and metabolism (HOMA-IR).

  Up to 6 months or at time of disease progression, whichever comes first

Study Arms (3)

Metastatic Pancreatic Adenocarcinoma (PDAC)

EXPERIMENTAL

30 patients with a diagnosis of 1st line metastatic or unresectable PDAC, CRC, or HCC and a BMI \>25 will receive GLP1 RA weekly + SOC treatment for 6 months or disease progression whichever comes first. SOC treatment for pancreatic cancer is modified FOLFIRINOX.

Drug: GLP1-RA (semaglutide)

Metastatic Colorectal Adenocarcinoma (CRC)

EXPERIMENTAL

10 patients with a diagnosis of 1st line metastatic or unresectable CRC and a BMI \>25 will receive GLP1 RA weekly + SOC treatment for 6 months or disease progression whichever comes first. SOC treatment for CRC is FOLFOX or FOLFIRI +/- bevacizumab.

Drug: GLP1-RA (semaglutide)

Metastatic Hepatocellular Carcinoma (HCC)

EXPERIMENTAL

10 patients with a diagnosis of 1st line metastatic or unresectable HCC and a BMI \>25 will receive GLP1 RA weekly + SOC treatment for 6 months or disease progression whichever comes first. SOC treatment for HCC is Tremelimumab/Durvalumab.

Drug: GLP1-RA (semaglutide)

Interventions

GLP1-RA (semaglutide) DRUG

Patients 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.

Metastatic Colorectal Adenocarcinoma (CRC); Metastatic Hepatocellular Carcinoma (HCC); Metastatic Pancreatic Adenocarcinoma (PDAC)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• SOC treatment as defined by NCCN® guidelines or institutional standard is allowable, however, options restricted to:
• Colorectal: FOLFOX or FOLIFIRI +/- bevacizumab
• Pancreatic: mFOLFIRINOX
• HCC: Tremelimumab/Durvalumab
• Patients are eligible who received prior perioperative chemotherapy for curative intent treatment and recurred ≥ 6 months since last dose of chemotherapy.
• ≥ 18 years old on day of consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate archival frozen or fixed tissue available from primary or metastatic site for genotypic analysis (at least 15 unstained slides and/or tumor block)
• Adequate hematologic and organ function laboratory values as follows:
• The ANC ≥ 1500/mm3 without colony stimulating factor support;
• Platelets ≥ 75,000/mm3;

You may not qualify if:

• 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.
• A personal or family history of medullary thyroid cancer (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2).
• A prior hypersensitivity reaction to semaglutide or any of the excipients in WEGOVY®. Serious hypersensitivity reaction, including anaphylaxis and angioedema, have been reported with WEGOVY®.
• Cachexia
• Subjects on insulin.
• Subjects with a history of diabetic retinopathy
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• o Cardiovascular disorders including:
• For patients being considered for bevacizumab (or bevacizumab biosimilar) only:
• Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;
• thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (eg, vena cava filter) within 6 months before the first dose of study treatment.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Colorectal Neoplasms; Carcinoma, Hepatocellular; Gastrointestinal Neoplasms

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases

Study Officials

• Aaron J Scott, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel EB Jarrett, MPH

CONTACT

5206260375; UACC-IIT@uacc.arizona.edu

Prisca Zimmerman

CONTACT

520-626-2548; priscaz@arizona.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Masking Description
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be assigned to an arm based on their cancer type. The only difference between arms is the SOC treatment.

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: June 4, 2026
• Study Start: July 10, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: July 2, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)