What is the mechanism of action of this treatment?

Common treatments for pancreatic cancer, such as Vemurafenib and Sorafenib, work by targeting specific molecular pathways involved in cancer cell growth and survival. Vemurafenib inhibits the BRAF protein, which is part of the MAPK/ERK signaling pathway often mutated in cancers, thereby reducing uncontrolled cell proliferation. Sorafenib, a multi-kinase inhibitor, targets several kinases involved in tumor growth and blood vessel formation, including RAF kinases, VEGFR, and PDGFR. These targeted therapies are significant for pancreatic cancer patients as they offer a more precise approach to treatment, potentially improving outcomes and reducing side effects compared to conventional chemotherapy.

What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, including chemotherapy regimens like gemcitabine and nab-paclitaxel, and targeted therapies such as Vemurafenib and Sorafenib, are associated with a range of side effects. Vemurafenib, a BRAF inhibitor, can cause skin reactions, joint pain, fatigue, and photosensitivity. Sorafenib, a multi-kinase inhibitor, may lead to hand-foot skin reactions, diarrhea, hypertension, and fatigue. Chemotherapy treatments like gemcitabine and nab-paclitaxel often result in nausea, fatigue, neutropenia, neuropathy, and diarrhea. These side effects vary in severity and frequency among patients.

What prior FDA approvals exist?

FDA-approved treatments for pancreatic cancer have primarily focused on chemotherapy regimens. However, targeted therapies similar to Vemurafenib and Sorafenib include drugs like Erlotinib, which targets the epidermal growth factor receptor (EGFR), and Sunitinib, approved for pancreatic neuroendocrine tumors, which inhibits multiple receptor tyrosine kinases. These treatments aim to target specific pathways involved in cancer cell growth and proliferation, similar to the mechanisms of action of Vemurafenib and Sorafenib.

What other types of research exist?

Promising novel alternatives for pancreatic cancer treatment include: 1) Aflibercept in combination with FOLFIRI, which has shown significant improvements in overall survival, progression-free survival, and response rate in metastatic colorectal cancer and is being explored for pancreatic cancer. 2) PARP inhibitors like Veliparib, especially for cancers with HR-DDR defects. 3) Targeted therapies such as Erlotinib, Cetuximab, and Bevacizumab, which have been studied in combination with Gemcitabine. 4) Immunotherapy agents like Durvalumab combined with chemotherapy, which are being investigated for their potential benefits.

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Kinase Inhibitor

Vemurafenib + Sorafenib for Pancreatic Cancer

Phase 2

Waitlist Available

Led By Erkut Borazanci, MD, MS

Research Sponsored by HonorHealth Research Institute

Eligibility Criteria Checklist

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

Must have

Be ≥ 18 years of age on day of signing informed consent.

Histologically confirmed cancer of the pancreas (KRAS mutated) with metastases and progression on at least ≥ 2 prior treatment regimens for their disease.

Must not have

Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Cycle 1/Day 1 or who has not recovered (i.e. NCI-CTC AE Version 5.0 ≤ Grade 1 at the time of signing informed consent) from adverse events due to a previously administered agent(s).

Patient with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v5.0 ≥ Grade 2 within 4 weeks before initiating study treatment; any other hemorrhage/bleeding event of NCI-CTCAE v5.0 ≥ Grade 3 within 4 weeks before initiating study treatment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up initiation of study treatment up to study completion, up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two types of cancer-fighting pills, Vemurafenib and Sorafenib, in patients with a specific type of pancreatic cancer. These patients have not improved with standard treatments. The pills work by blocking signals that help the cancer cells grow. Sorafenib is an oral multiple kinase inhibitor that has been approved for the treatment of advanced liver and kidney cancers.

Who is the study for?

This trial is for adults over 18 with KRAS mutated pancreatic cancer that has spread and worsened after at least two prior treatments. Participants must be able to take oral meds, have good organ function, not be pregnant or breastfeeding, agree to use contraception, and have no major health issues that could interfere with the study.

What is being tested?

The trial tests Vemurafenib and Sorafenib's effectiveness in treating advanced pancreatic cancer with a specific mutation. These are oral chemotherapy drugs given to those who haven't responded well to standard treatments.

What are the potential side effects?

Potential side effects of Vemurafenib and Sorafenib may include fatigue, skin reactions, digestive problems, liver issues, high blood pressure, bleeding risks, heart rhythm changes (QT prolongation), and increased risk of infections.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My pancreatic cancer has spread, is KRAS mutated, and has not responded to at least 2 treatments.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I can swallow and keep down pills.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't had cancer treatment in the last 2 weeks and have recovered from past treatment side effects.

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I have not had serious lung bleeding or any severe bleeding in the last month.

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I am not allergic to sorafenib, vemurafenib, or any related drugs.

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I am currently being treated for an infection.

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I have a history of bleeding or clotting disorders.

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I have seizures that are not controlled by medication.

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I have been diagnosed with Neurofibromatosis Type 1 or a similar condition.

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I have previously used a BRAF inhibitor like vemurafenib.

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I haven't taken any medications that affect heart rhythm recently.

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I haven't taken strong medication that affects liver enzymes in the last 28 days.

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I am able to follow the study's requirements and attend all follow-up visits.

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I have a wound, ulcer, or bone fracture that is not healing.

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I do not have any serious heart conditions.

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I have had an organ transplant.

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I have had pneumonitis treated with steroids or have it now.

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I have had significant surgery on my stomach or intestines.

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My high blood pressure is not controlled even with medication.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ initiation of study treatment up to study completion, up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~initiation of study treatment up to study completion, up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and initiation of study treatment up to study completion, up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Disease Control Rate of Vemurafenib in Combination with Sorafenib

Secondary study objectives

Confirm the Incidences of Adverse Events of Vemurafenib in Combination with Sorafenib

Measure circulating ctDNA

Measure phospho ERK and phospho AKT in plasma

Other study objectives

Clinical Activity of Vemurafenib in Combination with Sorafenib

Awards & Highlights

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Vemurafenib in Combination with SorafenibExperimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Sorafenib

2014

Completed Phase 3

~1670

Vemurafenib

2015

Completed Phase 3

~3550

0 / 21Eligibility criteria met

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

Common treatments for pancreatic cancer, such as Vemurafenib and Sorafenib, work by targeting specific molecular pathways involved in cancer cell growth and survival. Vemurafenib inhibits the BRAF protein, which is part of the MAPK/ERK signaling pathway often mutated in cancers, thereby reducing uncontrolled cell proliferation. Sorafenib, a multi-kinase inhibitor, targets several kinases involved in tumor growth and blood vessel formation, including RAF kinases, VEGFR, and PDGFR. These targeted therapies are significant for pancreatic cancer patients as they offer a more precise approach to treatment, potentially improving outcomes and reducing side effects compared to conventional chemotherapy.

MiR-338-5p Inhibits EGF-Induced EMT in Pancreatic Cancer Cells by Targeting EGFR/ERK Signaling.Current and future strategies for combined-modality therapy in pancreatic cancer.