Stage III Pancreatic Cancer AJCC v8Phase 1NCT04158635
Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer
A Phase 1 study testing Bosentan, Gemcitabine and Nab-paclitaxel in people with Stage III Pancreatic Cancer AJCC v8 and Stage IV Pancreatic Cancer AJCC v8, run by City of Hope Medical Center at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Pancreatic Carcinoma
- What is being tested?
- Bosentan, Gemcitabine and Nab-paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2021to 9 Mar 2027
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Main Inclusion Criteria
- Adult patients with unresectable pancreatic carcinoma
- Patients must be a candidate to receive one of the following chemotherapy combinations as determined by the treating physician:
Arm A2: gemcitabine plus nab-paclitaxel given every 2 weeks (arm A1 is closed per this amendment)
Arm B: mFOLFIRINOX given every 2 weeks
- Willingness to permit study team to obtain and use archival tissue, if already existing, or, be willing to undergo a fresh tumor biopsy if clinically possible (exceptions may be provided by study PI if medically unsafe to perform biopsy).
- Weight ≥ 40 kg
- ANC ≥ 1500/mm3; platelets ≥ 100,000/mm3
- AST, ALT ≤ 1.5 x ULN. Patients with liver metastases ≤ 3 x ULN
- Total serum bilirubin ≤ 1.5 x ULN
- Creatinine clearence ≥ 60 mL/min
Main Exclusion Criteria
- Current or planned use of Warfarin, Cyclosporine A, Rifampicin, Glyburide (other diabetic medications are allowed)
- Current or planned use of agents contraindicated for use with strong CYP3A4 inducers
- Strong inhibitors or inducers of CYP2C9
- Strong inhibitors or inducers of CYP3A
- Agent or agents that moderately inhibit both CYP2C9 and CYP3A (via a single concomitant agent, or co-administration of concomitant agents)
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.
- Current or history of ≥ Grade 2 peripheral neuropathy
- Known allergy to eggs or any of the components within the study agents and/or their excipients.
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: A Phase 1 Study of Gemcitabine, Nab-Paclitaxel, and Bosentan in Patients With 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.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess the safety, toxicity and feasibility of administering bosentan with nab-paclitaxel and gemcitabine.
SECONDARY OBJECTIVES:
- 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:
- 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.
- 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.
- Conditions
- Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Pancreatic Carcinoma
- Being tested
- Bosentan, Gemcitabine, Nab-paclitaxel, Quality-of-Life Assessment, Questionnaire Administration
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BosentanDrug
Also called Bosentan Monohydrate, Ro 47-0203, Tracleer
Given PO
GemcitabineDrug
Also called dFdC, dFdCyd, Difluorodeoxycytidine
Given IV
Nab-paclitaxelDrug
Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel
Given IV
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9 | Experimental | 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. Receives: Drug: Bosentan; Drug: Gemcitabine; Drug: Nab-paclitaxel; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12 | Experimental | 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. Receives: Drug: Bosentan; Drug: Gemcitabine; Drug: Nab-paclitaxel; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 | Experimental | 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. Receives: Drug: Bosentan; Drug: Gemcitabine; Drug: Nab-paclitaxel; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0.
Measured: 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.
Measured: Up to 21 days (Cycle 1)
Compliance
Number of bosentan tablets and bottles returned will be reconciled with the patient diary.
Measured: During the first week
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Time to treatment termination for any reason (progression, toxicity, death, patient preference), assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start1 Sep 2021
- Primary completion9 Mar 2027 (estimated)
- Study completion9 Mar 2027 (estimated)
Why it stopped: Accrual Goal met
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage III Pancreatic Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ravi Salgia, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04158635
- Sponsor's protocol ID
- 21314
- Other IDs
- NCI-2021-06609, 19312
- Status last verified
- Jun 2026
- First submitted
- 7 Nov 2019
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Gemcitabine, Nab-Paclitaxel, and Bosentan in Patients With Unresectable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT04158635
- Acronym / sponsor ID
- 21314
- Conditions
- Stage III Pancreatic Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8, Unresectable Pancreatic Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Accrual Goal met
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Sep 2021 (actual)
- Primary completion
- 9 Mar 2027 (estimated)
- Study completion
- 9 Mar 2027 (estimated)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To assess the safety, toxicity and feasibility of administering bosentan with nab-paclitaxel and gemcitabine.
SECONDARY OBJECTIVES:
- 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:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9 | Experimental | Drug: Bosentan, Drug: Gemcitabine, Drug: Nab-paclitaxel, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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 (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12 | Experimental | Drug: Bosentan, Drug: Gemcitabine, Drug: Nab-paclitaxel, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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. |
| Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 | Experimental | Drug: Bosentan, Drug: Gemcitabine, Drug: Nab-paclitaxel, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BosentanAlso: Bosentan Monohydrate, Ro 47-0203, TracleerGiven PO | Drug | Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 |
| GemcitabineAlso: dFdC, dFdCyd, DifluorodeoxycytidineGiven IV | Drug | Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 |
| Nab-paclitaxelAlso: ABI 007, ABI-007, Abraxane, Albumin-bound PaclitaxelGiven IV | Drug | Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 |
| Questionnaire AdministrationAncillary studies | Other | Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12, Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21 |
Primary outcome
Incidence of adverse events
Time frame: Up to 30 days after last dose of protocol therapy
Will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0.
Dose limiting toxicities (DLTs)
Time frame: Up to 21 days (Cycle 1)
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.
Compliance
Time frame: During the first week
Number of bosentan tablets and bottles returned will be reconciled with the patient diary.
3 secondary outcomes
Progression-free survival (PFS)
Time frame: Time to disease progression/ relapse or death as a result of any cause, assessed up to 2 years
Overall survival (OS)
Time frame: Time to death as a result of any cause, assessed up to 2 years
Time to treatment failure (TTF)
Time frame: Time to treatment termination for any reason (progression, toxicity, death, patient preference), assessed up to 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi Salgia principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bosentan, Gemcitabine and Nab-paclitaxel in people with Stage III Pancreatic Cancer AJCC v8 and Stage IV Pancreatic Cancer AJCC v8, run by City of Hope Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 30 days after last dose of protocol therapy). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.