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

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of cancer drugs to determine the best dose and monitor side effects in patients with metastatic pancreatic cancer or inoperable solid tumors. The drugs under study—Vismodegib (GDC-0449), Erlotinib Hydrochloride, and Gemcitabine Hydrochloride—aim to kill cancer cells or inhibit their growth. Participants must have a type of pancreatic cancer or solid tumor unsuitable for surgery or other standard treatments. This trial targets those who have declined standard treatment or exhausted other options. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to receive potentially groundbreaking therapy.

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.

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

Research has shown that the combination of vismodegib and erlotinib is generally manageable for patients. In earlier studies, patients taking these drugs together often experienced stable cancer for a few treatment cycles, indicating the drugs helped prevent the cancer from worsening temporarily. Although some patients did not see significant changes in their overall condition, most did not experience severe side effects.

Some patients in the study also took gemcitabine, a well-known cancer treatment with established safety. When all three drugs were used together, the combination remained manageable for patients.

Overall, while the drugs may not dramatically alter the disease for everyone, they have been shown to be safe enough for use in clinical trials, suggesting the treatment is unlikely to cause serious harm for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for pancreatic cancer, which typically involve chemotherapy drugs like gemcitabine, the investigational treatment with Vismodegib and Erlotinib offers a unique mechanism of action. Researchers are excited about these treatments because Vismodegib targets the Hedgehog signaling pathway, which is thought to play a role in the growth of cancer cells. Erlotinib adds another layer by inhibiting EGFR, a protein that helps cancer cells grow and divide. This combination could potentially offer a more comprehensive attack on cancer cells, making it a promising option for patients who may not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that a combination of three drugs—vismodegib, erlotinib, and gemcitabine—might help destroy more cancer cells in pancreatic cancer. In this trial, some participants will receive vismodegib and erlotinib, while others will also receive gemcitabine. Erlotinib blocks certain proteins that cancer cells need to grow. Studies indicate that this drug combination is generally well-tolerated, but it hasn't yet significantly impacted patients with advanced pancreatic cancer. However, some patients have experienced stable disease for several treatment cycles. These early results are promising, but more research is needed to confirm the treatment's effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Charles Erlichman

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/31787526/

Phase 1 trial of Vismodegib and Erlotinib combination in ...

Vismodegib and Erlotinib combination was well-tolerated although overall outcome in patients with metastatic PDAC was not significantly impacted by ...

2.

mayo.edu

mayo.edu/research/clinical-trials/cls-20314519

A Study of GDC-0449 and Erlotinib Hydrochloride, with or ...

Giving GDC-0449 together with erlotinib hydrochloride with or without gemcitabine hydrochloride may kill more tumor cells. Participation eligibility.

3.

withpower.com

withpower.com/trial/vismodegib-erlotinib---gemcitabine-for-pancreatic-cancer-48f4c

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

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 ...

4.

trial.medpath.com

trial.medpath.com/clinical-trial/e410041a0e2dd988/gdc-0449-erlotinib-gemcitabine-pancreatic-cancer

GDC-0449 and Erlotinib Hydrochloride With or Without ...

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 ...

5.

researchgate.net

researchgate.net/publication/313948651_Phase_I_trial_erlotinib_gemcitabine_and_the_hedgehog_inhibitor_GDC-0449

Phase I trial erlotinib, gemcitabine, and the hedgehog ...

Two patients receiving vismodegib and erlotinib experienced stable disease for 2 and 5 cycles, respectively. This regimen was well tolerated, ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4254161/

Pilot Clinical Trial of Hedgehog Pathway Inhibitor GDC ...

This report summarizes the efficacy, safety and biomarker results for 25 patients enrolled on this study. Patients and Methods. Eligibility.