A Phase 1 interventional study of Bosentan and Gemcitabine in Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8 and Unresectable Pancreatic Carcinoma, sponsored by City of Hope Medical Center. Suspended at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-15.
Sponsored by City of Hope Medical Center · Phase 1, Interventional, and Treatment
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.
3,235 studies on the registry are indexed under Pancreatic Neoplasms; 899 are open to participants now.
This study's planned enrollment of 21 is below the median of 46 across 2,424 interventional studies indexed under Pancreatic Neoplasms.
Browse Pancreatic Neoplasms studies →City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.
Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.
Counted across the registry records on this site, refreshed daily.
Main Inclusion Criteria
Arm A2: gemcitabine plus nab-paclitaxel given every 2 weeks (arm A1 is closed per this amendment)
Arm B: mFOLFIRINOX given every 2 weeks
Main Exclusion Criteria
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.
Drug: Bosentan · Drug: Gemcitabine · Drug: Nab-paclitaxel · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
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.
Drug: Bosentan · Drug: Gemcitabine · Drug: Nab-paclitaxel · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
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.
Drug: Bosentan · Drug: Gemcitabine · Drug: Nab-paclitaxel · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
Given PO
Also known as: Bosentan Monohydrate, Ro 47-0203, Tracleer
Given IV
Also known as: dFdC, dFdCyd, Difluorodeoxycytidine
Given IV
Also known as: ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel, Albumin-Stabilized Nanoparticle Paclitaxel, Nanoparticle Albumin-bound Paclitaxel, Nanoparticle Paclitaxel, Paclitaxel Albumin, paclitaxel albumin-stabilized nanoparticle formulation, protein-bound paclitaxel
Ancillary studies
Also known as: Quality of Life Assessment
Ancillary studies
Incidence of adverse events
Will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0.
Time frame: 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.
Time frame: Up to 21 days (Cycle 1)
Compliance
Number of bosentan tablets and bottles returned will be reconciled with the patient diary.
Time frame: During the first week
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 frame: 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 frame: 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 frame: Time to treatment termination for any reason (progression, toxicity, death, patient preference), assessed up to 2 years
Temporal impact of bosentan therapy on tumor vs. normal pancreatic tissue perfusion profile (tumor stroma and blood flow)
Time frame: Up to 2 years
Levels of nab-paclitaxel, bosentan and active plasma metabolite Ro 48-5033
Will be quantitated in the peripheral blood.
Time frame: Up to 2 years
Analysis of loci that encode organic anion transporting polypeptides (OATP) in participants who experience severe hepatotoxicity, increased during protocol therapy
Time frame: Up to 2 years
Quantification of the number of circulating tumor cells and temporal proteomic/micro ribonucleic acid (miRNA) profile will assess response to therapy
Time frame: Up to 2 years
Histopathology/ structural assessment and quantification of the miRNA profile
Will allow the identification of prognostic biomarkers.
Time frame: Up to 2 years
Quality of life assessment
Assesses using Functional Assessment of Cancer Therapy: General (FACT-G) questionnaire.
Time frame: Up to 2 years
This study is suspended, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
City of Hope Medical Center