Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04158635 |
|
Recruitment Status :
Recruiting
First Posted : November 12, 2019
Last Update Posted : November 25, 2022
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Stage III Pancreatic Cancer AJCC v8 Stage IV Pancreatic Cancer AJCC v8 Unresectable Pancreatic Carcinoma | Drug: Bosentan Drug: Gemcitabine Drug: Nab-paclitaxel Other: Quality-of-Life Assessment Other: Questionnaire Administration | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 21 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1 Study of Gemcitabine, Nab-Paclitaxel, and Bosentan in Patients With Unresectable Pancreatic Cancer |
| Actual Study Start Date : | September 1, 2021 |
| Estimated Primary Completion Date : | December 31, 2023 |
| Estimated Study Completion Date : | December 31, 2023 |
| 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 disease progression or unacceptable toxicity. |
Drug: Bosentan
Given PO
Other Names:
Drug: Gemcitabine Given IV
Other Names:
Drug: Nab-paclitaxel Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies |
|
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 progression or unacceptable toxicity. |
Drug: Bosentan
Given PO
Other Names:
Drug: Gemcitabine Given IV
Other Names:
Drug: Nab-paclitaxel Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies |
|
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 disease progression or unacceptable toxicity. |
Drug: Bosentan
Given PO
Other Names:
Drug: Gemcitabine Given IV
Other Names:
Drug: Nab-paclitaxel Given IV
Other Names:
Other: Quality-of-Life Assessment Ancillary studies
Other Name: Quality of Life Assessment Other: Questionnaire Administration Ancillary studies |
- 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.
- Progression-free survival (PFS) [ Time Frame: Time to disease progression/ relapse or death as a result of any cause, assessed up to 2 years ]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.
- Overall survival (OS) [ Time Frame: Time to death as a result of any cause, assessed up to 2 years ]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 failure (TTF) [ Time Frame: Time to treatment termination for any reason (progression, toxicity, death, patient preference), assessed up to 2 years ]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.
- 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 [ Time Frame: Up to 2 years ]Will be quantitated in the peripheral blood.
- 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 [ Time Frame: Up to 2 years ]Will allow the identification of prognostic biomarkers.
- Quality of life assessment [ Time Frame: Up to 2 years ]Assesses using Functional Assessment of Cancer Therapy: General (FACT-G) questionnaire.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04158635
| United States, California | |
| City of Hope Medical Center | Recruiting |
| Duarte, California, United States, 91010 | |
| Contact: Ravi Salgia 626-218-3712 rsalgia@coh.org | |
| Principal Investigator: Ravi Salgia | |
| Principal Investigator: | Ravi Salgia | City of Hope Medical Center |
| Responsible Party: | City of Hope Medical Center |
| ClinicalTrials.gov Identifier: | NCT04158635 |
| Other Study ID Numbers: |
21314 NCI-2021-06609 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 19312 ( Other Identifier: City of Hope Medical Center ) |
| First Posted: | November 12, 2019 Key Record Dates |
| Last Update Posted: | November 25, 2022 |
| Last Verified: | November 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Endocrine Gland Neoplasms Digestive System Diseases Pancreatic Diseases Endocrine System Diseases Gemcitabine Paclitaxel Albumin-Bound Paclitaxel Bosentan Antineoplastic Agents, Phytogenic Antineoplastic Agents |
Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antihypertensive Agents Endothelin Receptor Antagonists |