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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| combination therapy with no MEKi | Other | This cohort will receive combination therapy with no MEKi. |
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| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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Subjects have advanced PDAC with KRAS G12R mutation.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mandana Kamgar, MD, MPH | Contact | 414-805-4600 | mkamgar@mcw.edu |
| Name | Affiliation | Role |
|---|---|---|
| Mandana Kamgar, MD, MPH | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Froedtert Hospital and the Medical College of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
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| combination therapy with MEKi-HCQ | Drug | This cohort will receive combination therapy with MEKi-HCQ. |
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| combination therapy with MEKi-EGFRi | Drug | This cohort will receive combination therapy with MEKi-EGFRi. |
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| combination therapy with MEKi. | Drug | This cohort will receive combination therapy with MEKi. |
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| 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 |
| ID | Term |
|---|---|
| D003131 | Combined Modality Therapy |
| D006886 | Hydroxychloroquine |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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