Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer

NCT04158635 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 21314NCI-2021-0660919312
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8; Unresectable Pancreatic Carcinoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Progression-free survival (PFS)

  Time to disease progression/ relapse or death as a result of any cause, assessed up to 2 years

• Overall survival (OS)

  Time to death as a result of any cause, assessed up to 2 years

• Time to treatment failure (TTF)

  Time to treatment termination for any reason (progression, toxicity, death, patient preference), assessed up to 2 years

Other Outcomes (6)

• Temporal impact of bosentan therapy on tumor vs. normal pancreatic tissue perfusion profile (tumor stroma and blood flow)

  Up to 2 years

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

  Up to 2 years

• Analysis of loci that encode organic anion transporting polypeptides (OATP) in participants who experience severe hepatotoxicity, increased during protocol therapy

  Up to 2 years

Study Arms (3)

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.

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.

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.

Drug: Bosentan; Drug: Gemcitabine; Drug: Nab-paclitaxel; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Bosentan DRUG

Given PO

Also known as: Bosentan Monohydrate, Ro 47-0203, Tracleer

Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9; Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12; Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

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-paclitaxel DRUG

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

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 Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

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 Administration OTHER

Ancillary studies

Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 1-9; Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 10-12; Treatment (bosentan, nab-paclitaxel, gemcitabine) - Participant 13-21

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Bosentan; Gemcitabine; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Taxes

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Economics; Health Care Economics and Organizations

Study Officials

• Ravi Salgia

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2019
• First Posted: November 12, 2019
• Study Start: September 1, 2021
• Primary Completion (Estimated): March 9, 2027
• Study Completion (Estimated): March 9, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)