Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen

Summary

A Phase 3, randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of paltusotine treatment vs placebo as well as the long-term safety of paltusotine in adults with carcinoid syndrome due to well-differentiated neuroendocrine tumors. The purpose of this study is to continue the evaluation of the safety, efficacy, and pharmacokinetics (PK) of paltusotine in participants with carcinoid syndrome.

Interventions

• Paltusotine · DRUG

  Experimental Drug: Randomized

• Placebo · DRUG

  Matching Placebo Drug: Randomized

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

* Male or female ≥18 years of age, at the time of Screening.
* Willing and able to comply with the study procedures as specified in the protocol, including at least 70% compliance with the study diary for the 2-week period.
* Documented carcinoid syndrome requiring medical therapy. Participants must exhibit symptoms of flushing with or without frequent BMs as follows:

  * For participants who are naïve/not currently treated with somatostatin receptors ligands (SRL), they must exhibit an average of \>1 flushing episode/day over a period of 14 days
  * For participants who will wash out from SRL treatment, they must be symptomatically controlled and exhibit an increase in daily average flushing episodes and an average of \>1 flushing episode/day over a period of 14 days during the Washout Period.
* Evaluable documentation of locally advanced or metastatic histopathologically confirmed well-differentiated neuroendocrine tumor(s) \[NETs\].
* No significant disease progression as assessed by the Investigator within the last 6 months before randomization.

Exclusion Criteria:

* Diarrhea attributed to any condition(s) other than carcinoid syndrome.
* Uncontrolled/severe diarrhea associated with significant volume contraction, dehydration, or hypotension.
* Requires second line treatments (eg, telotristat) for control of carcinoid syndrome symptoms in the opinion of the Investigator.
* Treatment with specific NET therapy \<4 weeks before Screening (such as everolimus or sunitinib) or hepatic embolization, radiotherapy, peptide receptor radionuclide therapy (PRRT), and/or tumor debulking \<12 weeks before Screening.
* Major surgery within 8 weeks before Screening.
* History of another primary malignancy \<3 years prior to the date of randomization, except for adequately treated basal or squamous cell carcinoma of the skin, cancer of the breast has been completely locally excised and carcinoma in situ of the cervix has also been resected, previously treated malignancy, if all treatment for that malignancy was completed at least 3 years prior to first dose of study treatment, and no current evidence of disease, concurrent malignancy determined to be clinically stable and not requiring treatment.
* Diabetes mellitus treated with insulin for less than 6 weeks prior to the study entry.
* Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5%
* Unable to administer short-acting (SA) octreotide (octreotide acetate injection), or prior nonresponse documented with somatostatin agonists.
* Clinically significant concomitant disease or indicator of disease that is not a result of the primary disease under study, including but not limited to cardiovascular disease, estimated glomerular filtration rate 2×upper limit of normal \[ULN\], and/or total bilirubin (TB) \>1.5×ULN. (Participants with previously diagnosed Gilbert's syndrome not accompanied by other hepatobiliary disorders and associated with TB
* Alcohol or drug abuse is not permitted at any time during the study
* Diagnosed with symptomatic cholelithiasis

Sites (67)

• Banner MD Anderson Cancer Center, Gilbert, Arizona · RECRUITING
• Hoag Memorial Hospital Presbyterian, Newport Beach, California · RECRUITING
• Yale University - New Haven Hospital - Yale Cancer Center, New Haven, Connecticut · RECRUITING
• University of Miami, Miami, Florida · RECRUITING
• Moffitt Cancer Center, Tampa, Florida · RECRUITING
• Winshop Cancer Institute - Emory University, Atlanta, Georgia · RECRUITING
• University of Iowa Health Care, Iowa City, Iowa · RECRUITING
• University of Kentucky Medical Center, Lexington, Kentucky · RECRUITING
• Louisiana State University Health Sciences, Metairie, Louisiana · RECRUITING
• Henry Ford Cancer - Detroit, Detroit, Michigan · RECRUITING
• Mayo Clinic, Rochester, Minnesota · RECRUITING
• Icahn School of Medicine at Mount Sinai, New York, New York · RECRUITING
• University Hospitals Cleveland Medical Center, Cleveland, Ohio · RECRUITING
• Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania · RECRUITING
• Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah · RECRUITING
• University of Virginia Comprehensive Cancer Center, Charlottesville, Virginia · RECRUITING
• Medical College of Wisconcin, Milwaukee, Wisconsin · RECRUITING
• Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo, Buenos Aires, Argentina · RECRUITING
• Sanatorio Guemes, Buenos Aires, Argentina · WITHDRAWN
• Centro de Endocrinologia y Diabetes Dr. A. Gutman ICM - Investigaciones, Buenos Aires, Argentina · RECRUITING
• Instituto Médico Especializado Alexander Fleming, Buenos Aires, Argentina · RECRUITING
• Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo, CABA, Argentina · RECRUITING
• Instituto Médico de la Fundación Estudios Clínicos, Santa Fe, Argentina · RECRUITING
• AC Camargo Cancer Center, São Paulo, Brazil, Brazil · RECRUITING
• Fundacao PIO XII - Hospital de Amor Barretos, Barretos, Brazil · RECRUITING
• Sociedade Literaria e Caritativa Santos Agostinho - Hospital Sao José, Criciúma, Brazil · RECRUITING
• Nucleo de Pesquisa e Desenvolvimento de Medicamentos (MPDM), Fortaleza, Brazil · RECRUITING
• Associacao Hospitalar Moinhos de Vento, Porto Alegre, Brazil · RECRUITING
• Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil · RECRUITING
• Clinical Universidad Catolica del Maule, Ltda, Maule, Chile, Chile · RECRUITING
• Centro de Oncologia de Precision, Santiago, Chile, Chile · RECRUITING
• CECIM-Centro de Estudios Cliicos e Investigaciones Medicas, Santiago, Chile · RECRUITING
• Hospital Universitario San Ignacio, Bogotá, DC, Colombia · RECRUITING
• Instituto Nacional de Cancerologia, Bogotá, DC, Colombia · RECRUITING
• CHRU Tours - Hopital Trousseau, Chambray-lès-Tours, France · RECRUITING
• Hopital Beaujun - APHP, Clichy, France · RECRUITING
• APHM- Hopital de la Timone, Marseille, France · RECRUITING
• Centre Hospitalier Universitaire Nantes, Nantes, France · RECRUITING
• Centre Antoine Lacassagne, Nice, France · RECRUITING
• CHU Bordeaux - Hopital Haut-Leveque, Pessac, France · RECRUITING
• Asklepios Kilnic St. Georg, Hamburg, Germany · RECRUITING
• Universitätsklinikum Marburg (UKGM), Marburg, Germany · RECRUITING
• Instituto Europeo di Oncologia, Milan, Italy · RECRUITING
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy · RECRUITING
• Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza Di Torino, Turin, Italy · RECRUITING
• Health Pharma Professional Research S.A de C.V., Mexico City, Mexico · RECRUITING
• Centro de Oncolégica VIVA, Mexico City, Mexico · RECRUITING
• Uniwersyteckie Centrum Kliniczne im. Prof K. Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach, Katowice, Poland · RECRUITING
• Centrum Diagnostyczno-Lecznicze ,,GAMMED", Warsaw, Poland · RECRUITING
• Wokskowy Instytut Medyczny - Panstwowy Instytut Badawczy, Centrum Wsparcia Badań Klinicznych, Warsaw, Poland · RECRUITING
• Institute of Oncology Bucharest, Bucharest, Romania · RECRUITING
• Institute of Oncology "Prof. Dr. Ion Chiricuta" Cluj Napoca, Cluj-Napoca, Romania · RECRUITING
• Hospital Universitari Vall d'Hebron, Barcelona, Spain · RECRUITING
• Hospital Universitario Ramon y Cajal, Madrid, Spain · RECRUITING
• Fundacion Jimenez Diaz University Hospital, Madrid, Spain · RECRUITING
• Hospital Universitario 12 de Octubre, Madrid, Spain · RECRUITING
• Hospital Universitario Virgen de la Victoria, Málaga, Spain · RECRUITING
• Hospital Universitario Virgen del Rocio, Seville, Spain · RECRUITING
• Hospital Universitario y Politecnico La Fe, Valencia, Spain · RECRUITING
• King's College Hospital, London, UK, United Kingdom · RECRUITING
• Oxford University Hospitals NHS Foundation Trust, Oxford, UK, United Kingdom · RECRUITING
• Queen Elizabeth Hospital Brimingham, Birmingham, United Kingdom · RECRUITING
• University Hospital of Wales, Cardiff, United Kingdom · RECRUITING
• The Beatson WOS Cancer Centre, Glasgow, United Kingdom · RECRUITING
• Royal Free Hospital, London, United Kingdom · RECRUITING
• NIHR Clinical Research Facility, Royal Hallamshire Hospital, Sheffield, United Kingdom · RECRUITING
• University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom · RECRUITING