Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Antihypertensive Agents

Gemcitabine

Paclitaxel

Bosentan

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Endothelin Receptor Antagonists

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.

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.

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.

Nab-paclitaxel

Quality-of-Life Assessment

Questionnaire Administration

Ravi Salgia

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.

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

A Phase 1 Study of Gemcitabine, Nab-Paclitaxel, and Bosentan in Patients With Unresectable Pancreatic Cancer

Will be quantitated in the peripheral blood.

Will allow the identification of prognostic biomarkers.

Assesses using Functional Assessment of Cancer Therapy: General (FACT-G) questionnaire.

Will be recorded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0.

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.

Number of bosentan tablets and bottles returned will be reconciled with the patient diary.

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.

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.

National Cancer Institute (NCI)

City of Hope Medical Center

Skin and Connective Tissue Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Dacarbazine

Placebo

Andjela Kusic-Pajic, MD

The study is designed as a multicenter, double blind, parallel-group, placebo-controlled, randomized, event driven Phase II study of DTIC with or without bosentan as first-line treatment in patients with stage IV melanoma.

This is a randomized, double-blind (1:1 bosentan : placebo) trial to evaluate the effect of bosentan in combination with DTIC on TTP or death in patients with metastatic melanoma stage IV.

The patients will receive study medication (bosentan or placebo) and DTIC for 35 weeks to 105 weeks; the study will be completed when 66 events (tumor progression, death due to underlying disease, other/additional anti-tumor therapy) have been observed.

Study drug will be administered orally, 500 mg twice a day. DTIC will be given once every three weeks in a dosage of 1000 mg/m2 intravenously (i.v.) or in accordance with the Institution's DTIC treatment protocol.

Effect of Bosentan in Patients With Metastatic Melanoma Treated With Dacarbazine (DTIC)

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Evaluate the Effect of Bosentan in Patients With Stage IV Metastatic Melanoma Treated With Dacarbazine

Actelion

3.2 mg/m² as a 1-hour i.v. infusion on Day 1.

* Bosentan: 125 mg (one film-coated tablet of 125 mg) orally (p.o.) twice daily in the morning and in the evening during the prior five consecutive days before the day of lurbinectedin infusion (Day 1), and once daily on Day 1 (before lurbinectedin infusion).
* Lurbinectedin: 3.2 mg/m² as a 1-hour i.v. infusion on Day 1 in first three patients. Dose for remaining five patients will depend on PK and safety outcomes in first three patients.

Lurbinectedin

Bosentan: 125 mg (one film-coated tablet of 125 mg) orally (p.o.) twice daily in the morning and in the evening during the prior five consecutive days before the day of lurbinectedin infusion (Day 1), and once daily on Day 1 (before lurbinectedin infusion).

Pharma Mar, S.A.

Dr. Tatiana Hernandez Guerrero

Dr Emiliano Calvo Aller

Cristian M. Fernández, MD

Rubin Lubomirov, MD, PhD

Prospective, open-label, two-way crossover, phase Ib drug-drug interaction study in patients with advanced solid tumors.

The study consisting of two lurbinectedin cycles, one cycle in combination with bosentan and one cycle as single agent (in different order depending on the study sequence), and one additional third cycle of lurbinectedin as a single agent for patients who meet the continuation criteria and obtain a clinical benefit after the first two cycles.

All patients will receive a maximum of three cycles: two consecutive cycles of lurbinectedin, one cycle with and one cycle without bosentan co-administration (in different order depending on the study Sequence 1 or Sequence 2 of treatment), followed by a third cycle with lurbinectedin alone (this last optional for patients with clinical benefit). Lurbinectedin will be administered as a 1-hour intravenous (i.v.) infusion every three weeks (q3wk) via a central or peripheral vein. The dose of lurbinectedin will be 3.2 mg/m² for all patients when administered with and without bosentan. If toxicity occurs, the appropriate intra-patient dose level (DL) reductions will be implemented in the subsequent cycle.

Patients will be randomized in a 1:1 ratio to Sequence 1 (TR: Test-Reference; lurbinectedin + bosentan in Cycle 1) or Sequence 2 (RT: reference-Test; lurbinectedin + bosentan in Cycle 2).

Patients will receive lurbinectedin until disease progression, unacceptable toxicity, consent withdrawal or while it is considered to be in their best interest.

Treatment with lurbinectedin outside this study could be continued under a Compassionate Use Agreement after the completion of the optional third study cycle.

Study to Evaluate the Effect of Bosentan on the Pharmacokinetics of Lurbinectedin in Patients With Advanced Solid Tumors

An Open-Label, Multicenter Study to Assess the Potential Effects of Bosentan (a Moderate CYP3A4 Inducer) on the Pharmacokinetics of Lurbinectedin (PM01183) in Patients With Advanced Solid Tumors

Pharmacokinetic analyses will be evaluated in plasma by standard non-compartmental methods, or population methods, if necessary.

Lurbinectedin disposition (distribution, metabolism and excretion) from a single blood sample

PharmaMar

Diseases and Abnormalities at or Before Birth

Hemangioma, Capillary

Port-Wine Stain

Hemangioma

Congenital Abnormalities

Skin Abnormalities

Neoplasms, Vascular Tissue

Anti-Inflammatory Agents

Antirheumatic Agents

Analgesics

Chrysarobin

Patients with PWS resistant to PDL treatment will be included. A test area of the PWS will be treated by pulsed dye laser (PDL) (λ= 595 nm, 7 mm spot diameter, τp= 1.5 ms, same energy density used at the last session for each subject). The treatment by Bosentan (twice daily :2 mg/kg and maximum 62,5 mg) will be given 1 day before the PDL irradiation (maximum area treated 100 cm2) and continued for 14 days. The clinical improvement of the lesions will be evaluated by comparing standardized pictures, 14 days after the end of the treatment by Bosentan which corresponds to 1 month after the laser PDL irradiation. The evaluation will be realized by 2 independent physicians blinded to the area treated or not. Hemoglobin and SGOT/SGPT will be controlled before and after the treatment by Bosentan.

Patients with PWS resistant to PDL treatment will be included. The treatment by Bosentan (twice daily :2 mg/kg and maximum 62,5 mg) will be given 1 day before the PDL irradiation (maximum area treated 100 cm2) and continued for 14 days. The clinical improvement of the lesions will be evaluated by comparing standardized pictures, 14 days after the end of the treatment by Bosentan which corresponds to 1 month after the laser PDL irradiation. The evaluation will be realized by 2 independent physicians blinded to the area treated or not. Hemoglobin and SGOT/SGPT will be controlled before and after the treatment by Bosentan.

A test area of the PWS will be treated by pulsed dye laser (PDL) (λ= 595 nm, 7 mm spot diameter, τp= 1.5 ms, same energy density used at the last session for each subject).

Pulsed dye laser (PDL)

PASSERON Thierry, Phd

Pulsed dye laser (PDL) is the gold standard treatment for port-wine stains (PWS). However, the outcomes are highly variable due to the new angiogenesis occurring after laser irradiation. Studies suggest that endothelin is involved in the neoangiogenesis that occurred after treatment of port-wine stains by PDL. The main objective of this pilot clinical trial is to evaluate the effectiveness and safety of an inhibitor of endothelin orally taken, the Bosentan, following PDL treatment. Four patients with facial port-wine stain resistant to the PDL treatment will be included. The treatment by Bosentan (2 mg/kg twice daily, maximum 62,5 mg twice daily) will be given one day before the PDL irradiation and continued for 14 days. Only one test area of PWS will be treated with PDL. The primary outcome measure will be an important or complete improvement (Investigator Global Assessment 3 or 4) between treated area and non treated one, 14 days after the end of the treatment which corresponds to one month after the laser PDL session. The evaluation will been performed on standardized pictures by 2 independent physicians blinded to the region treated or not.

Pulsed dye laser (PDL) is the gold standard treatment for port-wine stains (PWS). However, the outcomes are highly variable due to the new angiogenesis occurring after laser irradiation. Studies suggest that endothelin is involved in the neoangiogenesis that occurred after treatment of port-wine stains by PDL . The main objective of this pilot clinical trial is to evaluate the effectiveness and safety of an inhibitor of endothelin orally taken, the Bosentan, following PDL treatment. Four patients with facial port-wine stain resistant to the PDL treatment will be included. The treatment by Bosentan (2 mg/kg twice daily, maximum 62,5 mg twice daily) will be given one day before the PDL irradiation (maximum surface 100 cm²) and continued for 14 days. Only one test area of PWS will be treated with PDL. The primary outcome measure will be an important or complete improvement (Investigator Global Assessment 3 or 4) between treated area and non treated one, 14 days after the end of the treatment which corresponds to one month after the laser PDL session. The evaluation will been performed on standardized pictures by 2 independent physicians blinded to the region treated or not.

Treatment of Resistant Port-wine Stains With Bosentan and Pulsed Dye Laser: a Pilot Study

Treatment of Port-wine Stains by Bosentan in Addition to Pulsed Dye Laser (PDL) in Children or Young Adults Who Previously Failed to Respond to PDL Alone: a Monocentric Pilot Study

The primary outcome measure will be an important or complete improvement (Investigator Global Assessment) between treated area and non treated one, at 1 month after the start of treatment by bosentan and Pulsed Dye Laser

The secondary outcome measure will be the satisfaction of the patients (or their parents), or the patient alone if major, about the efficiency and the safety of the treatments at 1 month after the start of treatment by bosentan and Pulsed Dye Laser. A visual analogical scale will be used.

Frequency, severity and occurrence of side effects will be noted.

The secondary outcome measure will be the satisfaction of the patients (or their parents), or the patient alone if major, about the safety of the treatments at 1 month after the start of treatment with bosentan and Pulsed Dye Laser

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer	NCT04158635	Stage III Pancr... Stage IV Pancre... Unresectable Pa...	Bosentan Gemcitabine Nab-paclitaxel Quality-of-Life... Questionnaire A...	18 Years -	City of Hope Medical Center
Effect of Bosentan in Patients With Metastatic Melanoma Treated With Dacarbazine (DTIC)	NCT01009177	Melanoma	Bosentan Placebo	18 Years - 70 Years	Actelion
Study to Evaluate the Effect of Bosentan on the Pharmacokinetics of Lurbinectedin in Patients With Advanced Solid Tumors	NCT05072106	Advanced Solid ...	Lurbinectedin Bosentan	18 Years -	PharmaMar
Treatment of Resistant Port-wine Stains With Bosentan and Pulsed Dye Laser: a Pilot Study	NCT02317679	Port-wine Stain...	Bosentan Pulsed dye lase...	7 Years - 60 Years	Centre Hospitalier Universitaire de Nice
Study to Evaluate the Effect of Bosentan on the Pharmacokinetics of Lurbinectedin in Patients With Advanced Solid Tumors	NCT05072106	Advanced Solid ...	Lurbinectedin Bosentan	18 Years -	PharmaMar

Spots Global Cancer Trial Database for bosentan

Every month we try and update this database with for bosentan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bosentan

Every month we try and update this database with for bosentan cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bosentan cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.