What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, such as MEK inhibitors (e.g., Cobimetinib), PARP inhibitors (e.g., Olaparib), ERK inhibitors (e.g., LY3214996), and PLK1 inhibitors (e.g., Onvansertib), are associated with a range of side effects. MEK inhibitors often cause gastrointestinal issues, skin rash, and cardiovascular effects. PARP inhibitors can lead to nausea, fatigue, anemia, and increased risk of myelodysplastic syndrome. ERK inhibitors may result in gastrointestinal disturbances, fatigue, and skin toxicity. PLK1 inhibitors are known to cause hematologic toxicities, including neutropenia and thrombocytopenia, as well as gastrointestinal symptoms. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, focusing on various mechanisms of action. Olaparib, a PARP inhibitor, has been approved for use in patients with germline BRCA-mutated metastatic pancreatic cancer who have been treated with chemotherapy. While specific approvals for Cobimetinib (MEK inhibitor), LY3214996 (ERK inhibitor), and Onvansertib (PLK1 inhibitor) in pancreatic cancer are not detailed, these drugs are being studied for their potential efficacy. Other approved treatments include chemotherapeutic agents like gemcitabine and nab-paclitaxel, as well as targeted therapies such as erlotinib, which inhibits the epidermal growth factor receptor (EGFR).

What other types of research exist?

Promising novel alternatives for pancreatic cancer treatment in 2024 include: 1) KRAS inhibitors such as sotorasib and adagrasib, which target the KRAS G12C mutation; 2) CDK4/6 inhibitors like palbociclib and ribociclib, which inhibit cell cycle progression; 3) Immunotherapy agents such as pembrolizumab (anti-PD-1) and nivolumab (anti-PD-1), which enhance the immune response against cancer cells; 4) FGFR inhibitors like erdafitinib for patients with FGFR mutations; and 5) Novel combinations of existing therapies, such as combining PARP inhibitors with immune checkpoint inhibitors or other targeted agents.

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MEK/ERK Inhibitor

Targeted Drug Therapy for Pancreatic Cancer

Phase < 1

Recruiting

Led By Charles D Lopez

Research Sponsored by OHSU Knight Cancer Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing four experimental drugs to see if they can help treat pancreatic cancer. The drugs work by blocking important processes that cancer cells need to grow and survive. The trial focuses on patients with pancreatic cancer who do not respond well to standard treatments. Gemcitabine was the first agent investigated for its potential to improve symptoms and overall well-being in pancreatic cancer patients.

Who is the study for?

Adults (18+) with pancreatic cancer, either resectable or metastatic adenocarcinoma, who can consent to treatment and biopsies. They may be new to treatment or have had prior therapy with a specific washout period. Good organ function is required, and they must not be pregnant or breastfeeding. Contraception use is necessary for participants of childbearing potential.

What is being tested?

The trial tests the effectiveness of cobimetinib, olaparib, LY3214996 (temuterkib), and onvansertib in treating pancreatic cancer by comparing tissue samples before and after treatment. It's an early phase I trial designed to inform future trials based on biomarkers.

What are the potential side effects?

Potential side effects include allergic reactions to the drugs' components, digestive issues due to oral administration challenges, increased risk of infection, blood disorders from bone marrow suppression, liver toxicity indicated by elevated enzymes levels in the blood.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Proportion of all pharmacodynamic feasibility-evaluable participants within a study arm that have a measurable change in post-treatment tumor biology from baseline

Secondary study objectives

Incidence of >= grade 3 toxicities for each assigned window treatment (as described in sub-protocol)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Group I: Arm VII (tremelimumab)Experimental Treatment1 Intervention

Patients receive tremelimumab IV over 60 minutes one-time. Within 12-24 hours of cycle completion, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Group II: Arm VI (AZD5305)Experimental Treatment1 Intervention

Patients receive AZD5305 PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Group III: Arm V (azenosertib)Experimental Treatment1 Intervention

Patients receive azenosertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Group IV: Arm IV (onvansertib)Experimental Treatment1 Intervention

Patients receive onvansertib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Group V: Arm II (cobimetinib)Experimental Treatment1 Intervention

Patients receive cobimetinib PO QD on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Group VI: Arm I (olaparib)Experimental Treatment1 Intervention

Patients receive olaparib PO BID on days 1-10 in the absence of disease progression or unacceptable toxicity. Within 12-24 hours, patients undergo biopsy or surgery as clinically appropriate per institutional standards for management of patient's disease.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Tremelimumab

2017

Completed Phase 2

~3070

Onvansertib

2017

Completed Phase 2

~220

Cobimetinib

2017

Completed Phase 3

~3630

Olaparib

2007

Completed Phase 4

~2190

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Cobimetinib is a MEK inhibitor that blocks the MEK/ERK pathway, which is often overactive in cancer cells, leading to uncontrolled growth. Olaparib is a PARP inhibitor that prevents cancer cells from repairing their DNA, causing them to die, especially effective in tumors with BRCA mutations. LY3214996 is an ERK inhibitor that targets the ERK protein, a downstream component of the MEK/ERK pathway, further inhibiting cancer cell proliferation. Onvansertib is a PLK1 inhibitor that disrupts cell division, leading to cancer cell death. These targeted therapies are important for pancreatic cancer patients as they offer more personalized and potentially more effective treatment options based on the specific characteristics of their cancer.