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

Sponsor

Mandana Kamgar, MD (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05630989

Collaborator

(none)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Ductal Adenocarcinoma	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 Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

40 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

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

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2025

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	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

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years.
Diagnosis of advanced pancreatic ductal adenocarcinoma as determined by the treating physician or tumor board.
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.
Ability to understand a written informed consent document and the willingness to sign it.