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

Recruiting

• Conditions: Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: combination therapy with MEKi-HCQ; Other: combination therapy with no MEKi; Drug: combination therapy with MEKi.; Drug: combination therapy with MEKi-EGFRi

• Registration Number: NCT05630989
• Lead Sponsor: Mandana Kamgar, MD

Brief Summary

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).

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 Timeline

• Study First Submitted: 2022-11-20
• Study First Submitted QC: 2022-11-29
• Study First Posted: 2022-11-30
• Study Start: 2023-02-07
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-24
• Primary Completion: 2027-08-01
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Therapy with MEKi- Hydroxychloroquine (HCQ)	combination therapy with MEKi-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.
Therapy with no MEKi	combination 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.
Therapy with MEKi-Other	combination therapy with 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 combination therapy with MEKi and a specified drug combination.
Therapy with MEKi- Epidermal growth factor receptor inhibitor (EGFRi)	combination therapy with MEKi-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.

Primary Outcome Measures

Name	Time	Method
The number of subjects with no progression.	6 months	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Froedtert Hospital and the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States