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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of three drugs to treat pancreatic cancer that has spread or cannot be surgically removed. The researchers aim to find the best dose and understand the side effects of gemcitabine (Gemzar), dasatinib (Sprycel), and erlotinib when used together. These drugs stop cancer cell growth in different ways. People with advanced pancreatic cancer who have not received gemcitabine in the last six months might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

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

Research shows that the combination of dasatinib, erlotinib, and gemcitabine is generally safe, with manageable side effects. In earlier studies, this combination showed promise for patients with advanced pancreatic cancer. Although patients experienced some side effects, they were usually manageable.

Dasatinib and erlotinib block certain proteins that help cancer cells grow. Gemcitabine, a chemotherapy drug, targets cancer cells, stopping them from dividing or killing them. These drugs have been tested together before, and while side effects can occur, they are usually not severe.

As a phase 1 trial, this study aims to find the best dose with the fewest side effects. This phase also assesses the treatment's safety. More detailed safety information will come from later trials. However, previous patients generally tolerated these drugs well when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for pancreatic cancer because it brings together three powerful drugs: dasatinib, erlotinib hydrochloride, and gemcitabine hydrochloride. Unlike standard treatments, which often rely solely on gemcitabine, this approach adds dasatinib, a tyrosine kinase inhibitor, and erlotinib, an epidermal growth factor receptor inhibitor, to target cancer cells in different ways. This multi-targeted strategy aims to enhance the overall effectiveness of treatment by not only attacking the cancer cells more aggressively but also potentially overcoming resistance that can develop with traditional therapies. The hope is that this combination could offer improved outcomes for patients with this challenging disease.

What evidence suggests that this combination chemotherapy might be an effective treatment for pancreatic cancer?

Research has shown that using gemcitabine, dasatinib, and erlotinib together may help treat pancreatic cancer. In this trial, participants will receive a combination of these three drugs. Gemcitabine kills cancer cells or stops them from dividing. Dasatinib and erlotinib block certain enzymes that cancer cells need to grow. Previous studies found that gemcitabine alone can help pancreatic cancer patients live for about two years on average. By combining these drugs, the researchers aim to improve results by attacking the cancer in different ways. This approach seeks to increase the chances of slowing down or stopping cancer growth. ^{1 2 3 6 7}

Who Is on the Research Team?

Dana Cardin

Principal Investigator

Vanderbilt University/Ingram Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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. clinicaltrials.gov clinicaltrials.gov/study/NCT01660971

Gemcitabine Hydrochloride, Dasatinib, and Erlotinib ... Dasatinib and erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4110498/

Current and future systemic treatment options in metastatic ... Median survival is 4 to 6 months and median 5-year survival is less than 5% (2). Great majority of the patients with pancreatic adenocarcinoma presents at ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01660971?term=erlotinib&aggFilters=status:rec%20enr%20act%20ava&viewType=Table&rank=7

Gemcitabine Hydrochloride, Dasatinib, and Erlotinib ... Types of outcome measures include primary outcome measure and secondary outcome measure. ... A type of intervention model describing a clinical trial in which two ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7913382/

The State-of-the-Art of Phase II/III Clinical Trials for Targeted ... Pre-clinical data have shown that combining bemcentinib with gemcitabine improved gemcitabine efficacy in several xenografts mouse modes of pancreatic cancer [ ...

5. mdpi.com mdpi.com/2072-6694/16/21/3564

Navigating Clinical Trials 1978–2024 for PDAC A 2019 study found that patients with pancreatic cancer treated with gemcitabine had a mean overall survival of 2 years and a 5-year survival rate of 15–20% [35] ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5891394/

Dual Src and EGFR Inhibition in Combination with ... Dasatinib, erlotinib, and gemcitabine was safe with manageable side effects, and with encouraging preliminary clinical activity in advanced pancreatic cancer.

7. go.drugbank.com go.drugbank.com/conditions/DBCOND0073917

Pancreatic Carcinoma Stage III (DBCOND0073917) - DrugBank Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery.