Combination Chemotherapy for Pancreatic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Ravi Salgia

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: City of Hope Medical Center

Must not be taking: Warfarin, Cyclosporine A, Rifampicin, Glyburide

Disqualifiers: Other cancers, Peripheral neuropathy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including Warfarin, Cyclosporine A, Rifampicin, Glyburide, and any drugs that strongly affect specific liver enzymes (CYP2C9 and CYP3A). Other diabetic medications are allowed.

What data supports the effectiveness of the drug combination of Bosentan, Tracleer, Gemcitabine, Gemzar, Nab-paclitaxel, ABI-007, nanoparticle albumin-bound paclitaxel, paclitaxel albumin-stabilized nanoparticle formulation, protein-bound paclitaxel, Abraxane, Pazenir for pancreatic cancer?

Research shows that combining nanoparticle albumin-bound paclitaxel with gemcitabine significantly improves survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. This combination has demonstrated substantial antitumor activity and is considered an evidence-based treatment for advanced pancreatic cancer.

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Is the combination chemotherapy of nab-paclitaxel and gemcitabine safe for humans?

The combination of nab-paclitaxel (Abraxane) and gemcitabine has been studied for safety in patients with advanced pancreatic cancer, including those with specific conditions like hyperbilirubinaemia (a liver condition causing high bilirubin levels). These studies suggest that the treatment is generally safe, but individual tolerability can vary, especially in elderly patients.

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What makes the combination chemotherapy with Bosentan, Gemcitabine, and Nab-paclitaxel unique for treating pancreatic cancer?

This treatment is unique because it combines Bosentan, a drug not typically used for pancreatic cancer, with Gemcitabine and Nab-paclitaxel, which are known to improve survival in advanced cases. The combination may offer a novel approach by potentially enhancing the effectiveness of standard chemotherapy regimens.

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Eligibility Criteria

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.

Inclusion Criteria

Agreement by females and males of childbearing potential to use an adequate method of birth control (hormonal contraception is inadequate) or abstain from heterosexual activity for the course of the study through 30 days after the last dose of study medication

My condition cannot be treated with surgery.

You are expected to live for more than 3 months.

Exclusion Criteria

I am not taking strong CYP3A inhibitors or inducers.

I am not taking Cyclosporine A or rifampicin.

Women who are or are planning to become pregnant or breastfeed

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive bosentan orally twice daily and nab-paclitaxel and gemcitabine intravenously on days 1, 8, and 15 of each 28-day cycle

Up to 2 years

Visits on days 1, 8, and 15 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days after last dose, then every 2 months until disease progression, then biannually

Participant Groups

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.

Group I: Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 Experimental Treatment 5 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 10-12 Experimental Treatment 5 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 1-9 Experimental Treatment 5 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.

Bosentan is already approved in European Union, United States, Canada, Switzerland, Japan for the following indications:

🇪🇺 Approved in European Union as Tracleer for:

• Pulmonary arterial hypertension

🇺🇸 Approved in United States as Tracleer for:

• Pulmonary arterial hypertension

🇨🇦 Approved in Canada as Tracleer for:

• Pulmonary arterial hypertension

🇨🇭 Approved in Switzerland as Tracleer for:

• Pulmonary arterial hypertension

🇯🇵 Approved in Japan as Tracleer for:

• Pulmonary arterial hypertension

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

City of Hope Medical Center Duarte, CA

Who Is Running the Clinical Trial?

City of Hope Medical Center Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

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

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. [2022] Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS.

2. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer suffering from cholestatic hyperbilirubinaemia-A retrospective analysis. [2022] Treatment of patients with advanced pancreatic carcinoma (APC) and hyperbilirubinaemia is problematic because these patients were regularly excluded from clinical studies. Nanoparticle albumin-bound paclitaxel and gemcitabine (nab-P/G) is an evidence-based treatment for patients with APC. This retrospective study investigated the safety and efficacy of nab-P/G in patients with APC and cholestatic hyperbilirubinaemia.

3. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022] Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma.

4. Japan pubmed.ncbi.nlm.nih.gov

A clinical trial to assess the feasibility and efficacy of nab-paclitaxel plus gemcitabine for elderly patients with unresectable advanced pancreatic cancer. [2022] The efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) plus gemcitabine (GEM) in elderly Japanese patients with pancreatic cancer remain unclear. Therefore, we prospectively investigated the tolerability and efficacy of nab-PTX + GEM in Japanese patients aged ≥ 75 years with non-curatively resectable pancreatic cancer.

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

Nab-Paclitaxel Plus S-1 Shows Increased Antitumor Activity in Patient-Derived Pancreatic Cancer Xenograft Mouse Models. [2017] To investigate the antitumor activity of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1 in patient-derived pancreatic cancer xenograft mouse models and to explore biomarkers that could predict drug efficacy.

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

Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. [2022] Abraxane (ABI-007) is a 130-nm albumin-bound (nab) particle formulation of paclitaxel, devoid of any additional excipients. We hypothesized that this change in formulation alters the systemic disposition of paclitaxel compared with conventional solvent-based formulations (sb-paclitaxel; Taxol), and leads to improved tolerability of the drug.

7. France pubmed.ncbi.nlm.nih.gov

Paclitaxel albumin-bound particles (abraxane) in combination with bevacizumab with or without gemcitabine: early experience at the University of Miami/Braman Family Breast Cancer Institute. [2022] Paclitaxel albumin-bound particles (nab-paclitaxel, ABRAXANE) (nab-P) improve outcomes when compared against single agent cremophor-based paclitaxel, as do the addition of bevacizumab (B) or gemcitabine (G) to the same agent. There are no available data regarding combinations of nab-P with B and/or G. Ongoing investigational efforts are evaluating various doublets with these agents, but, to the best of our knowledge, not all 3 of them in the same regimen. All drugs are currently FDA-approved in the treatment of cancer.

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

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022] In a phase 1-2 trial of albumin-bound paclitaxel (nab-paclitaxel) plus gemcitabine, substantial clinical activity was noted in patients with advanced pancreatic cancer. We conducted a phase 3 study of the efficacy and safety of the combination versus gemcitabine monotherapy in patients with metastatic pancreatic cancer.

9. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant nab-paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single-arm phase II study (NAC-GA trial). [2023] Nab-paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab-paclitaxel plus gemcitabine (GnP-NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear.