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2021-09-01
2026-01-27
2026-01-27
21
NCT04158635
City of Hope Medical Center
City of Hope Medical Center
INTERVENTIONAL
Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer
This phase I trial studies the side effects and best dose of bosentan and how well it works when given together with gemcitabine and nab-paclitaxel for the treatment of pancreatic cancer that cannot be removed by surgery (unresectable). Bosentan may block the hormone endothelin and prevent the growth and spread of pancreatic cancer. Drugs used in chemotherapy, such as gemcitabine and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bosentan with chemotherapy (gemcitabine and nab-paclitaxel) may work better in treating patients with pancreatic cancer compared to chemotherapy alone.
PRIMARY OBJECTIVE: I. To assess the safety, toxicity and feasibility of administering bosentan with nab-paclitaxel and gemcitabine. SECONDARY OBJECTIVES: I. To assess the response rate associated with this combination therapy in first line pancreatic cancer patients. II. To assess the progression-free survival and overall survival of all patients who start protocol therapy, and describe the outcomes based on measures of compliance during the lead-in week, and compliance with supplement during chemotherapy. EXPLORATORY OBJECTIVES: I. To determine the impact of bosentan on the mass transport in the tumor (surrogate of alterations in tumor stroma and blood flow). (Pharmacodynamic Investigations) II. To describe the pharmacokinetic profile of nab-paclitaxel and bosentan and compare to historic single-agent profile. (Pharmacokinetic Investigations) III. To explore the association between hepatotoxicity to study agents and organic anion-transporting polypeptide (OATP) polymorphisms. (Pharmacogenomic Investigations) IV. To explore biomarkers on pre-treatment biopsy samples and peripheral blood samples for correlations of predictive of response. V. To describe quality of life utilizing the Functional Assessment of Cancer Therapy: General (FACT-G) questionnaire. OUTLINE: Patients receive bosentan orally (PO) twice daily (BID) on days -7 to 21 or 8-21 of cycle 1 and days 1-21 of subsequent cycles. Patients also receive nab-paclitaxel intravenously (IV) over 30 minutes and gemcitabine IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days. Patients who complete study treatment without disease progression are followed up every 2 months until disease progression and then biannually thereafter. Patients who complete study treatment with disease progression are followed up biannually.
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
| Study Registration Dates | Results Reporting Dates | Study Record Updates |
|---|---|---|
2019-11-07 | N/A | 2025-08-18 |
2019-11-07 | N/A | 2025-08-19 |
2019-11-12 | N/A | 2025-08 |
This section provides details of the study plan, including how the study is designed and what the study is measuring.
Primary Purpose:
Treatment
Allocation:
Non Randomized
Interventional Model:
Single Group
Masking:
None
Arms and Interventions
| Participant Group/Arm | Intervention/Treatment |
|---|---|
| EXPERIMENTAL: Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9 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 di | DRUG: Bosentan
DRUG: Gemcitabine
DRUG: Nab-paclitaxel
OTHER: Quality-of-Life Assessment
OTHER: Questionnaire Administration
|
| EXPERIMENTAL: Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12 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 p | DRUG: Bosentan
DRUG: Gemcitabine
DRUG: Nab-paclitaxel
OTHER: Quality-of-Life Assessment
OTHER: Questionnaire Administration
|
| EXPERIMENTAL: Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 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 di | DRUG: Bosentan
DRUG: Gemcitabine
DRUG: Nab-paclitaxel
OTHER: Quality-of-Life Assessment
OTHER: Questionnaire Administration
|
| Primary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Incidence of adverse events | Will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0. | Up to 30 days after last dose of protocol therapy |
| Dose limiting toxicities (DLTs) | Toxicities will be graded according to NCI CTCAE v 4.0. DLT's apply only to bosentan-only single stage AND cycle 1 and should be attributable to the treatment. | Up to 21 days (Cycle 1) |
| Compliance | Number of bosentan tablets and bottles returned will be reconciled with the patient diary. | During the first week |
| Secondary Outcome Measures | Measure Description | Time Frame |
|---|---|---|
| Progression-free survival (PFS) | Will be evaluated using the Kaplan-Meier methods, both as a single group and by disease classification (metastatic versus [vs.] advanced unresectable). Response will also be examined by disease classification as part of a secondary analysis. | Time to disease progression/ relapse or death as a result of any cause, assessed up to 2 years |
| Overall survival (OS) | Will be evaluated using the Kaplan-Meier methods, both as a single group and by disease classification (metastatic vs. advanced unresectable). Response will also be examined by disease classification as part of a secondary analysis. | Time to death as a result of any cause, assessed up to 2 years |
| Time to treatment failure (TTF) | Will be evaluated using the Kaplan-Meier methods, both as a single group and by disease classification (metastatic vs. advanced unresectable). Response will also be examined by disease classification as part of a secondary analysis. | Time to treatment termination for any reason (progression, toxicity, death, patient preference), assessed up to 2 years |
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.
Ages Eligible for Study:
ALL
Sexes Eligible for Study:
18 Years
Accepts Healthy Volunteers:
This is where you will find people and organizations involved with this study.
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
No publications available
