Vemurafenib + Sorafenib for Pancreatic Cancer

Overseen By Erkut Borazanci, MD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: HonorHealth Research Institute

Must not be taking: BRAF inhibitors, QTc prolongation drugs

Disqualifiers: CNS metastases, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two oral chemotherapy drugs, Vemurafenib and Sorafenib, to determine their effectiveness in treating a specific type of pancreatic cancer with a KRAS mutation that has worsened despite standard treatments. The goal is to assess whether these drugs can slow or reduce the cancer's progression. This trial suits individuals with this type of pancreatic cancer who have tried at least two other treatment plans and can take oral medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that can prolong the QTc interval or cause Torsades de Pointe (a type of heart rhythm problem) within 14 days before starting the trial and during the study. Also, you must stop taking strong or moderate CYP3A inducers or inhibitors 28 days before starting the trial and during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Vemurafenib and Sorafenib have undergone safety testing in humans. When used together, these drugs are usually well-tolerated. Some individuals have experienced side effects such as rash, tiredness, and diarrhea, which are common with many cancer treatments.

Vemurafenib has been used for other cancers and is known to be safe. Sorafenib is also approved for other cancers, which reassures about its safety. However, when combined, monitoring for any new side effects is important.

For those considering joining this trial, it's helpful to know that these drugs are not completely new. However, participating in a trial means there might still be unknowns. Always consult a healthcare professional about any concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Vemurafenib and Sorafenib for pancreatic cancer because these drugs target specific mutations in cancer cells, potentially leading to more effective treatment outcomes. Unlike standard treatments like chemotherapy, which attacks all rapidly dividing cells, Vemurafenib specifically targets the BRAF mutation, and Sorafenib inhibits multiple kinases involved in tumor growth. This precision in targeting could mean fewer side effects and improved effectiveness, offering new hope for patients with limited options.

What evidence suggests that Vemurafenib and Sorafenib could be effective for pancreatic cancer?

Studies have shown that using Vemurafenib and Sorafenib together can help treat certain types of cancer by targeting specific genetic changes. This trial will evaluate the effectiveness of this combination for pancreatic cancer with KRAS mutations. Early research suggests this combination might extend survival, with an average survival time of about 4 months. However, some patients experienced serious side effects, such as blood clots. Vemurafenib, often used for other cancers with similar genetic changes, has shown promising early results. While this suggests potential effectiveness, the treatment also carries risks that require careful consideration. ^{1 2 4 5 6}

Who Is on the Research Team?

Erkut Borazanci, MD, MS

Principal Investigator

HonorHealth Research Institute

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I know my cancer's KRAS and BRAF mutation status or have a sample for testing.

My organs are functioning well.

Be able to understand and be willing to sign the written informed consent for the trial. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.

Exclusion Criteria

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

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

I have stable brain metastases and haven't used steroids in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Vemurafenib and Sorafenib for 16 weeks to assess disease control rate

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for overall survival and adverse events

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Sorafenib
• Vemurafenib

Trial Overview 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.

How Is the Trial Designed?

Group I: Vemurafenib in Combination with Sorafenib Experimental Treatment 2 Interventions

Sorafenib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma
• Radioactive iodine-refractory differentiated thyroid carcinoma

Approved in Canada as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Nexavar for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Who Is Running the Clinical Trial?

HonorHealth Research Institute

Lead Sponsor

Trials

26

Recruited

940+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a phase II trial involving 17 patients with advanced pancreatic cancer, the combination of sorafenib and gemcitabine showed no objective responses, with only 18% of patients achieving stable disease.

The treatment resulted in a median overall survival of 4.0 months and was associated with significant toxicities, including thrombosis in 18% of patients, indicating that this combination is not effective for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Kindler, HL., Wroblewski, K., Wallace, JA., et al.[2022]

Vemurafenib, an oral BRAF kinase inhibitor, has been shown to be a safe and tolerable treatment for patients with metastatic melanoma harboring BRAFV600 mutations, with a median follow-up of 32.2 months in a study involving 3219 patients.

The most common adverse events included arthralgia, alopecia, and hyperkeratosis, and while patients with longer durations of response experienced more severe adverse events, no new safety concerns emerged over the two-year treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label, multicentre safety study of vemurafenib in 3219 patients with BRAFV600 mutation-positive metastatic melanoma: 2-year follow-up data and long-term responders' analysis. Blank, CU., Larkin, J., Arance, AM., et al.[2022]

Sorafenib is an oral kinase inhibitor that effectively targets multiple tyrosine kinases involved in cancer, including pathways like raf-ras and VEGF, which are often disrupted in tumors.

The FDA has approved sorafenib for advanced renal cell cancer and hepatocellular cancer, and it has shown promising clinical activity in thyroid cancer, with ongoing trials exploring its use in combination therapies for various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib. Hasskarl, J.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05068752

Phase II Trial of Vemurafenib and Sorafenib in Pancreatic ... The purpose of this research is to determine the benefit of two oral chemotherapy drugs, Vemurafenib and Sorafenib, in individuals with KRAS mutated pancreatic ...

2. aacrjournals.org aacrjournals.org/cancerres/article/84/17_Supplement_2/A002/747526/Abstract-A002-Phase-II-Trial-of-Vemurafenib

Abstract A002: Phase II Trial of Vemurafenib + Sorafenib in ... Phase II Trial of Vemurafenib + Sorafenib in Advanced KRAS Mutated Pancreas Cancer [abstract]. In: Proceedings of the AACR Special Conference in ...

3. withpower.com withpower.com/trial/phase-3-pancreatic-neoplasms-8-2021-d0281

Vemurafenib + Sorafenib for Pancreatic Cancer The treatment resulted in a median overall survival of 4.0 months and was associated with significant toxicities, including thrombosis in 18% of patients, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9938883/

BRAF v600E–mutant cancers treated with vemurafenib ... In this VEM + PLUS study, we sought to analyze the clinical outcomes of patients previously treated with these agents when combined with BRAF ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2211124724010611

Cell-specific models reveal conformation-specific RAF ... In mutant BRAF cancers, clinically used RAF inhibitors (RAFi), such as vemurafenib and encorafenib, show substantial initial response rates.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05068752?term=AREA%5BBasicSearch%5D(vemurafenib)%20AND%20AREA%5BOverallStatus%5D(RECRUITING%20OR%20ENROLLING_BY_INVITATION%20OR%20ACTIVE_NOT_RECRUITING%20OR%20AVAILABLE)&rank=5

Phase II Trial of Vemurafenib and Sorafenib in Pancreatic Cancer A phase of research to describe clinical trials that gather more information about a drug's safety and effectiveness by studying different populations and ...