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

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Albumin-Bound Paclitaxel; Bosentan; Gemcitabine; Paclitaxel

Criteria

Inclusion Criteria:

• Documented informed consent by the participant

• Willingness to permit study team to obtain and use archival tissue, if already existing

• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Life expectancy of > 3 months

• Histologic diagnosis of pancreatic carcinoma

• Unresectable disease

• Patients must not have received prior chemotherapy for disease with the following exceptions:

• Gemcitabine with or without capecitabine or fluorouracil, irinotecan, leucovorin, and oxaliplatin (FOLFIRINOX) in the adjuvant setting if the recurrence is greater than 6 months from the completion of chemotherapy

• Radiation sensitizing doses of 5-fluorouracil or capecitabine are allowed as part of adjuvant treatment and recurrence must be documented >= 6 months from the completion of chemotherapy

• 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

• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

• Absolute neutrophil count (ANC) >= 1,500/mm^3 (performed within 14 days prior to day 1 of bosentan)

• Platelets >= 100,000/mm^3 (performed within 14 days prior to day 1 of bosentan)

• Total serum bilirubin =< 1.5 x upper limit of normal (ULN) (performed within 14 days prior to day 1 of bosentan)

• Aspartate aminotransferase (AST) =< 1.5 x ULN or =< 3 x ULN with liver metastases (performed within 14 days prior to day 1 of bosentan)

• Alanine aminotransferase (ALT) =< 1.5 x ULN or =< 3 x ULN with liver metastases (performed within 14 days prior to day 1 of bosentan)

• Creatinine clearance of >= 60 mL/min per 24 hour urine or the Cockcroft-Gault (performed within 14 days prior to day 1 of bosentan)

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

• If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

Exclusion Criteria:

• Dietary/herbal supplements

• Other investigational products

• Warfarin

• Cyclosporine A or rifampicin

• Glyburide; other hypoglycemic agents may be permitted

• 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)

• Current or history of >= grade 2 peripheral neuropathy

• Issues with tolerating oral medication (e.g. inability to swallow pills, malabsorption issues, ongoing nausea or vomiting)

• Women who are or are planning to become pregnant or breastfeed

• Known allergy to eggs or any of the components within the study agents and/or their excipients

• 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 three years

• Intercurrent or historic medical condition that increases subject risk in the opinion of the investigator. Eligibility may be revisited for intercurrent medical conditions once resolution/recovery is deemed adequate by the investigator (e.g. recovery from major surgery, completion of treatment for severe infection)

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)