A Registry to Capture Patient Outcomes With KRAS G12R Altered Advanced Pancreatic Ductal Adenocarcinoma Treated With MEK Inhibitor-based Combination Therapy

This is an observational precision oncology study designed to collect and analyze data that allows us to characterize the safety and efficacy of several different mitogen-activated protein kinase kinase inhibitor (MEKi) -based treatment strategies and the feasibility of administering MEKi combination therapies to patients with KRAS G12R mutated advanced pancreatic ductal adenocarcinoma (PDAC).

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Other: combination therapy with no MEKi; Drug: combination therapy with MEKi-HCQ; Drug: combination therapy with MEKi-EGFRi; Drug: combination therapy with MEKi.

Detailed Description

Patient medical records, obtained both retrospectively and prospectively, will be examined for results of molecular profiling obtained through standard of care testing to help understand how well KRAS G12R pancreatic patients respond to MEKi-based combination matched therapy. Patient outcome parameters including but not limited to tumor response, patient survival, and toxicity will be analyzed. Moreover, metrics will be collected to ascertain whether a future clinical trial involving a MEKi-based combination therapy is feasible to carry out.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Mandana Kamgar, MD, MPH; Phone Number: 414-805-4600; Email: mkamgar@mcw.edu

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Froedtert Hospital and the Medical College of Wisconsin
      • Contact: Mandana Kamgar, MD; Phone Number: 414-805-4600; Email: mkamgar@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects have advanced PDAC with KRAS G12R mutation.

Description

Inclusion Criteria:

1. Age ≥18 years.
2. Diagnosis of advanced pancreatic ductal adenocarcinoma as determined by the treating physician or tumor board.
3. Tumor must have KRAS G12R mutation, as determined by a next generation sequencing (NGS) panel or circulating tumor DNA panel of choice of the treating physician.
4. Ability to understand a written informed consent document and the willingness to sign it.

Exclusion Criteria:

1. Age <18 years.
2. Primary cancer diagnosis other than advanced pancreatic ductal adenocarcinoma
3. Tumor does not have a KRAS G12R mutation.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Therapy with no MEKi; Subjects have advanced PDAC with KRAS G12R mutation. Subjects' tumors must have KRAS G12R mutation, as determined by a next generation sequencing (NGS) panel or circulating tumor DNA panel of choice of the treating physician. Subjects will receive therapy with no MEKi.	Other: combination therapy with no MEKi; This cohort will receive combination therapy with no MEKi.; Other Names: mitogen-activated extracellular signal-regulated kinase inhibitor
Therapy with MEKi- Hydroxychloroquine (HCQ); Subjects have advanced PDAC with KRAS G12R mutation. Subjects' tumors must have KRAS G12R mutation, as determined by a next generation sequencing (NGS) panel or circulating tumor DNA panel of choice of the treating physician. Subjects will receive therapy with MEKi and HCQ.	Drug: combination therapy with MEKi-HCQ; This cohort will receive combination therapy with MEKi-HCQ.; Other Names: mitogen-activated extracellular signal-regulated kinase inhibitor with hydroxychloroquine
Therapy with MEKi- Epidermal growth factor receptor inhibitor (EGFRi); Subjects have advanced PDAC with KRAS G12R mutation. Subjects' tumors must have KRAS G12R mutation, as determined by a next generation sequencing (NGS) panel or circulating tumor DNA panel of choice of the treating physician. Subjects will receive combination therapy with MEKi and EGFRi.	Drug: combination therapy with MEKi-EGFRi; This cohort will receive combination therapy with MEKi-EGFRi.; Other Names: mitogen-activated extracellular signal-regulated kinase inhibitor with epidermal growth factor receptor inhibitor
Therapy with MEKi-Other; Subjects have advanced PDAC with KRAS G12R mutation. Subjects' tumors must have KRAS G12R mutation, as determined by a next generation sequencing (NGS) panel or circulating tumor DNA panel of choice of the treating physician. Subjects will receive combination therapy with MEKi and a specified drug combination.	Drug: combination therapy with MEKi.; This cohort will receive combination therapy with MEKi.; Other Names: mitogen-activated extracellular signal-regulated kinase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of subjects with no progression.	This is defined as the time from the start of treatment until six months on treatment, or disease progression, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death, whichever occurs first.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of subjects who have a complete response.	A complete response will be determined using RECIST v1.1.	2 years
The number of subjects who have a partial response.	A partial response will be determined using RECIST v1.1.	2 years
The number of grade 3 adverse events at least possibly related to a drug.	Adverse events and serious adverse events will be classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.	2 years
The number of grade 4 adverse events at least possibly related to a drug.	Adverse events and serious adverse events will be classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.	2 years

Collaborators and Investigators

• Sponsor: Mandana Kamgar, MD
• Investigators: Principal Investigator: Mandana Kamgar, MD, MPH, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: November 20, 2022
• First Submitted That Met QC Criteria: November 29, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pancreatic Ductal Adenocarcinoma; Precision medicine; KRAS G12R mutation; Retrospective Chart Review; Prospective Chart Review
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Quinolines; Aminoquinolines; Chloroquine; Hydroxychloroquine; Combined Modality Therapy
• Other Study ID Numbers: PRO00045718

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No