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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug combination Vemurafenib and Sorafenib for pancreatic cancer?

In a study, 57% of pancreatic cancer patients treated with sorafenib and another drug achieved stable disease, suggesting some potential benefit. Additionally, sorafenib has shown activity against various tumors, indicating it might help in treating pancreatic cancer. ^{1 2 3 4 5}

What safety information is available for Vemurafenib and Sorafenib?

Sorafenib has been associated with rare cases of acute pancreatitis (inflammation of the pancreas) and should be discontinued if this occurs. Vemurafenib can cause side effects like joint pain, rash, and fatigue, and in some cases, it has led to liver issues, including severe liver damage. ^{3 6 7 8 9}

What makes the drug combination of Vemurafenib and Sorafenib unique for treating pancreatic cancer?

The combination of Vemurafenib and Sorafenib is unique because it targets multiple pathways often deregulated in cancer, such as the B-raf and VEGF pathways, which are not typically addressed by standard pancreatic cancer treatments. This approach aims to inhibit cancer growth more effectively by attacking the cancer cells on multiple fronts. ^{1 4 5 7 10}

Research Team

Erkut Borazanci, MD, MS

Principal Investigator

HonorHealth Research Institute

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. United States 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. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Multiple colon ulcerations, perforation and death during treatment of malignant melanoma with sorafenib. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Sorafenib for the treatment of unresectable hepatocellular carcinoma. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Sorafenib. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Acute pancreatitis associated with sorafenib. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study. [2022]

8. England 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Vemurafenib-induced granulomatous hepatitis. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Sorafenib: targeting multiple tyrosine kinases in cancer. [2018]