Combination Chemotherapy for Pancreatic Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inducers/inhibitors

Disqualifiers: Brain metastases, Immune deficiency, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle

19 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain investigational agents or medications that affect liver enzymes. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination of erlotinib and 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) that is often overactive in pancreatic cancer, helping to slow down the growth of cancer cells. ^{1 2 3 4 5}

Is the combination of dasatinib, erlotinib, and gemcitabine safe for humans?

The combination of dasatinib, erlotinib, and gemcitabine has been found to be safe with manageable side effects in humans, with common side effects including mild to moderate anemia (low red blood cell count), fatigue, nausea, and changes in blood cell counts. ^{4 6 7 8 9}

What makes the combination chemotherapy with Dasatinib, Erlotinib Hydrochloride, and Gemcitabine Hydrochloride unique for pancreatic cancer?

This combination therapy is unique because it includes Dasatinib, which is not commonly used in standard treatments for pancreatic cancer. Erlotinib, a part of this combination, is a targeted therapy that blocks specific proteins involved in cancer growth, and when combined with Gemcitabine, it has shown a small increase in survival compared to Gemcitabine alone. ^{1 4 10 11 12}

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and dasatinib when given together with erlotinib hydrochloride in treating patients with pancreatic cancer that has spread to other places in the body or cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Dasatinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine hydrochloride and dasatinib together with erlotinib hydrochloride may kill more tumor cells.

Research Team

Dana Cardin

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Eligibility Criteria

This trial is for adults with pancreatic cancer that has spread or can't be surgically removed. They may have had previous chemotherapy, but not with gemcitabine unless it was over 6 months ago. Participants need to have a life expectancy over 3 months, normal kidney function or specific clearance levels, and must use contraception if applicable. They should be able to swallow pills and have certain blood cell counts within specified ranges.

Inclusion Criteria

It's been over 4 weeks since my last radiation dose, and I have measurable cancer outside the treated area.

Your white blood cell count is at least 3,000 per microliter.

Your blood platelet count is at least 100,000 per microliter.

Exclusion Criteria

I am not taking strong drugs that affect liver enzyme CYP3A4.

I haven't had chemotherapy or radiotherapy in the last 4-6 weeks and have recovered from any side effects.

I am not pregnant and will stop breastfeeding if treated with erlotinib or dasatinib.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive gemcitabine hydrochloride IV on days 1, 8, and 15, and dasatinib and erlotinib hydrochloride orally daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

3 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 4 weeks.

30 days initially, then every 4 weeks

Treatment Details

Interventions

• Dasatinib
• Erlotinib Hydrochloride
• Gemcitabine Hydrochloride

Trial Overview The trial tests the combination of gemcitabine hydrochloride (chemotherapy) with dasatinib and erlotinib hydrochloride (enzyme blockers) in treating advanced pancreatic cancer. It aims to find the safest doses and observe how well these drugs work together to stop tumor growth by killing cells or preventing them from dividing.

Participant Groups

Group I: Treatment (gemcitabine, dasatinib, erlotinib) Experimental Treatment 3 Interventions

Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1, 8, and 15, and dasatinib PO QD and erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in European Union as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in Canada as Sprycel for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

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

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

2. 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]

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. Italy pubmed.ncbi.nlm.nih.gov

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

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

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

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

Dual Src and EGFR inhibition in combination with gemcitabine in advanced pancreatic cancer: phase I results : A phase I clinical trial. [2023]

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

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

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

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

9. England pubmed.ncbi.nlm.nih.gov

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

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

Recent progress and limitations of chemotherapy for pancreatic and biliary tract cancers. [2021]

11. Australia pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine, erlotinib and S-1 in patients with advanced pancreatic cancer. [2021]

12. Italy pubmed.ncbi.nlm.nih.gov

First-line treatment for advanced pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011. [2022]