Vismodegib + Erlotinib (+/- Gemcitabine) for Pancreatic Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Uncontrolled illness, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days per course

55 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial is studying the side effects and best dose of erlotinib hydrochloride when given together with GDC-0449 with or without gemcitabine hydrochloride in treating patients with metastatic pancreatic cancer or solid tumors that cannot be removed by surgery. Drugs used in chemotherapy, such as GDC-0449 and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving GDC-0449 together with erlotinib hydrochloride with or without gemcitabine hydrochloride may kill more tumor cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does exclude participants who are currently on a CYP3A4 inhibitor or inducer. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

What data supports the effectiveness of the drug combination Vismodegib + Erlotinib (+/- Gemcitabine) for pancreatic cancer?

Research shows that combining erlotinib with gemcitabine can slightly improve survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. Erlotinib targets a specific protein (epidermal growth factor receptor) involved in cancer growth, and this combination has shown anti-tumor activity in studies. ^{1 2 3 4 5}

What is known about the safety of Vismodegib, Erlotinib, and Gemcitabine for pancreatic cancer?

Erlotinib, when used with gemcitabine for pancreatic cancer, can cause side effects like diarrhea, rash, dry skin, and hair loss. These side effects are generally less severe than those from traditional chemotherapy. The combination of these drugs has been studied and is considered safe for use in treating pancreatic cancer, although patients may experience some discomfort from the side effects. ^{2 6 7 8 9}

How is the drug Vismodegib + Erlotinib (+/- Gemcitabine) unique for treating pancreatic cancer?

This treatment is unique because it combines Vismodegib, a drug that targets a specific pathway involved in cancer growth, with Erlotinib, which blocks signals that help cancer cells grow, and optionally Gemcitabine, a standard chemotherapy drug. This combination aims to improve outcomes by attacking the cancer from multiple angles, potentially offering a new option for patients with pancreatic cancer. ^{2 9 10 11 12}

Research Team

Charles Erlichman

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with metastatic pancreatic cancer or solid tumors that can't be surgically removed. They must not have curative standard therapy options, agree to use effective contraception, abstain from smoking, and be able to take oral medication. Excluded are those who've had certain recent treatments, uncontrolled illnesses, CNS metastases unless stable, pregnant/nursing women, or inadequate organ function.

Inclusion Criteria

You need to have a certain amount of a type of white blood cell called neutrophils in your blood.

My solid tumor cannot be surgically removed, has no other treatment options, or I refuse standard treatments.

My pancreatic cancer has spread and can be biopsied.

Exclusion Criteria

There is a known treatment that could cure or extend my life.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Criterion: You cannot have received certain types of treatments within specific time frames before the study. You also cannot have certain medical conditions or be taking certain medications. Additionally, if you are pregnant, nursing, or not using reliable birth control, you cannot participate. If you have certain heart conditions, eye abnormalities, or have had specific prior treatments, you may not be eligible to participate.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Hedgehog antagonist GDC-0449 and erlotinib hydrochloride orally once daily on days 1-28. Some patients also receive gemcitabine hydrochloride intravenously on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per course

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, including adverse events and response assessment.

3 months

Treatment Details

Interventions

• Erlotinib Hydrochloride
• GDC-0449
• Gemcitabine Hydrochloride

Trial Overview The study tests the side effects and optimal doses of erlotinib hydrochloride combined with GDC-0449 (vismodegib), with or without gemcitabine hydrochloride in patients. These drugs aim to stop tumor growth by killing cells or preventing cell division and blocking enzymes needed for cell growth.

Participant Groups

Group I: Treatment (vismodegib, erlotinib hydrochloride, gemcitabine) Experimental Treatment 4 Interventions

Patients receive Hedgehog antagonist GDC-0449 PO QD and erlotinib hydrochloride PO QD on days 1-28. Some patients also receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

A combination of gemcitabine and erlotinib has been shown to provide a survival advantage in patients with locally advanced and metastatic pancreatic cancer compared to gemcitabine alone, highlighting its efficacy in a disease known for poor outcomes.

Erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor, demonstrates anti-tumor activity when used alongside gemcitabine, suggesting a promising mechanism of action in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of erlotinib in the management of pancreatic cancer. Starling, N., Neoptolemos, J., Cunningham, D.[2021]

References

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

Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Role of erlotinib in the management of pancreatic cancer. [2021]

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

Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. [2023]

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

Impact of epidermal growth factor receptor (EGFR) kinase mutations, EGFR gene amplifications, and KRAS mutations on survival of pancreatic adenocarcinoma. [2018]

5. China pubmed.ncbi.nlm.nih.gov

[Efficacy of gemcitabine combined with erlotinib in patients with advanced pancreatic cancer]. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Erlotinib-induced episcleritis in a patient with pancreatic cancer. [2015]

7. England pubmed.ncbi.nlm.nih.gov

Erlotinib: success of a molecularly targeted agent for the treatment of advanced pancreatic cancer. [2018]

8. England pubmed.ncbi.nlm.nih.gov

A phase II study of erlotinib in gemcitabine refractory advanced pancreatic cancer. [2022]

9. Italy pubmed.ncbi.nlm.nih.gov

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice. [2022]

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

Erlotinib/gemcitabine for first-line treatment of locally advanced or metastatic adenocarcinoma of the pancreas. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Vandetanib plus gemcitabine versus placebo plus gemcitabine in locally advanced or metastatic pancreatic carcinoma (ViP): a prospective, randomised, double-blind, multicentre phase 2 trial. [2022]

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

A phase II trial of erlotinib in combination with gemcitabine and capecitabine in previously untreated metastatic/recurrent pancreatic cancer: combined analysis with translational research. [2022]