What side effects are associated with this type of intervention?

The most common treatments for pancreatic cancer, particularly those involving gemcitabine and nab-paclitaxel, are associated with several side effects. Gemcitabine can cause fatigue, nausea, vomiting, and neutropenia (a decrease in white blood cells). Nab-paclitaxel is known to cause neuropathy (nerve damage), myelosuppression (bone marrow suppression), and gastrointestinal symptoms such as nausea and diarrhea. When combined with Bosentan, an endothelin blocker, additional side effects may include hepatotoxicity (liver damage) and peripheral edema (swelling of the extremities). Patients undergoing these treatments should be closely monitored for these adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, including gemcitabine and nab-paclitaxel. Gemcitabine, a nucleoside analog, has been a cornerstone in the treatment of pancreatic cancer for many years. Nab-paclitaxel, an albumin-bound formulation of paclitaxel, is often used in combination with gemcitabine to improve outcomes. While Bosentan, an endothelin receptor antagonist, is currently being studied in combination with these drugs, it has not yet received FDA approval for the treatment of pancreatic cancer.

What other types of research exist?

Promising novel alternatives to Bosentan for pancreatic cancer patients include the combination of gemcitabine and nab-paclitaxel with other targeted therapies or immunotherapies. For instance, ongoing research is exploring the efficacy of combining these chemotherapies with agents like pembrolizumab (an immunotherapy) or novel molecular targeted agents. Additionally, trials involving MEK inhibitors like trametinib, which have shown potential in other cancers, may also be considered.

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Endothelin Receptor Antagonist

Combination Chemotherapy for Pancreatic Cancer

Phase 1

Recruiting

Led By Ravi Salgia

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Unresectable disease

Histologic diagnosis of pancreatic carcinoma

Must not have

Strong inhibitors or inducers of CYP3A

Cyclosporine A or rifampicin

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of three drugs for patients with pancreatic cancer that cannot be surgically removed. One drug blocks a hormone to stop cancer growth, while the other two drugs kill cancer cells or prevent them from multiplying. One of these drugs has been widely used in pancreatic cancer treatment, often in combination with other drugs to improve effectiveness.

Who is the study for?

This trial is for adults with pancreatic cancer that can't be surgically removed. They must not have had prior chemotherapy, except certain types in the adjuvant setting if recurrence occurred after 6 months. Participants need functioning major organs, no severe allergies to study drugs or their components, and agree to use effective birth control methods.

What is being tested?

The trial tests bosentan combined with gemcitabine and nab-paclitaxel chemotherapy to see if it's more effective for treating unresectable pancreatic cancer than chemotherapy alone. It also aims to determine the best dose of bosentan and assess its side effects when used with these chemotherapies.

What are the potential side effects?

Potential side effects include those common to chemotherapy such as nausea, fatigue, hair loss, blood cell count changes leading to increased infection risk or bleeding problems. Bosentan may cause liver issues or headaches. The combination could increase the chance of experiencing these effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition cannot be treated with surgery.

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I have been diagnosed with pancreatic cancer.

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My kidney function, measured by creatinine clearance, is good.

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I can take care of myself and perform daily activities.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am not taking strong CYP3A inhibitors or inducers.

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I am not taking Cyclosporine A or rifampicin.

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I am not taking strong drugs that affect liver enzyme CYP2C9.

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I am not using, nor plan to use, drugs that strongly affect liver enzyme CYP3A4.

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I have or had nerve damage in my hands or feet that is moderate or worse.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Compliance

Dose limiting toxicities (DLTs)

Incidence of adverse events

Secondary study objectives

Overall survival (OS)

Progression-free survival (PFS)

Time to treatment failure (TTF)

Other study objectives

Histopathology/ structural assessment and quantification of the miRNA profile

Levels of nab-paclitaxel, bosentan and active plasma metabolite Ro 48-5033

Quality of life assessment

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21Experimental Treatment5 Interventions

Patients receive bosentan PO BID on days 1-21 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12Experimental Treatment5 Interventions

Patients receive bosentan PO BID on days -7 to 21 and days 1-21 of subsequent cycles. Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group III: Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9Experimental Treatment5 Interventions

Patients receive bosentan PO BID on days 8-21 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive nab-paclitaxel IV over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nab-paclitaxel

2014

Completed Phase 3

~1950

Gemcitabine

2017

Completed Phase 3

~1920

Bosentan

2010

Completed Phase 4

~1530

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for pancreatic cancer include gemcitabine, nab-paclitaxel, and bosentan. Gemcitabine is a nucleoside analog that inhibits DNA synthesis, leading to cell death. Nab-paclitaxel is a formulation of paclitaxel bound to albumin, which stabilizes microtubules and prevents cell division. Bosentan, an endothelin receptor antagonist, blocks the action of endothelin-1, a molecule that promotes tumor growth and spread. These mechanisms are crucial as they target different aspects of cancer cell survival and proliferation, potentially improving treatment efficacy when used in combination.

TRPM2 promotes pancreatic cancer by PKC/MAPK pathway.