Carcinoid Syndrome Efficacy Study Featuring an Oral Daily Paltusotine Regimen

Official title

A Randomized, Parallel Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Paltusotine in Adults With Carcinoid Syndrome Due to Well-Differentiated Neuroendocrine Tumors

Overview

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.

Detailed description

This is a global, randomized, parallel-group, placebo-controlled study to evaluate the efficacy and safety of paltusotine in adults with carcinoid syndrome. The study includes a screening period of up to 11 weeks, a double-blinded randomized control period of 16 weeks, an open label extension period of 104 weeks, and a follow-up period of 4 weeks.

Interventions

• Drug Paltusotine
  Experimental Drug: Randomized
• Drug Placebo
  Matching Placebo Drug: Randomized

Primary outcome measures

• Participants will record the number of flushing per day in a daily diary to assess the efficacy of paltusotine vs placebo in reducing flushing episodes. [Time frame: Measured at Week 12]

Secondary outcome measures (1)

• Participants will record the number of bowel movements (BMs) per day in a daily diary to assess the efficacy of paltusotine vs placebo in reducing BMs/day. [Time frame: Measured at Week 12]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 17 centers

• Banner MD Anderson Cancer Center — Gilbert
• Hoag Memorial Hospital Presbyterian — Newport Beach
• Yale University - New Haven Hospital - Yale Cancer Center — New Haven
• University of Miami — Miami
• Moffitt Cancer Center — Tampa
• Winshop Cancer Institute - Emory University — Atlanta
• University of Iowa Health Care — Iowa City
• University of Kentucky Medical Center — Lexington
• … and 9 more centers

United Kingdom · 8 centers

• King's College Hospital — London
• Oxford University Hospitals NHS Foundation Trust — Oxford
• Queen Elizabeth Hospital Brimingham — Birmingham
• University Hospital of Wales — Cardiff
• The Beatson WOS Cancer Centre — Glasgow
• Royal Free Hospital — London
• NIHR Clinical Research Facility, Royal Hallamshire Hospital — Sheffield
• University Hospital Southampton NHS Foundation Trust — Southampton

Spain · 7 centers

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Universitario Ramon y Cajal — Madrid
• Fundacion Jimenez Diaz University Hospital — Madrid
• Hospital Universitario 12 de Octubre — Madrid
• Hospital Universitario Virgen de la Victoria — Málaga
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Universitario y Politecnico La Fe — Valencia

Argentina · 6 centers

• Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo — Buenos Aires
• Sanatorio Guemes — Buenos Aires
• Centro de Endocrinologia y Diabetes Dr. A. Gutman ICM - Investigaciones — Buenos Aires
• Instituto Médico Especializado Alexander Fleming — Buenos Aires
• Hospital de Gastroenterologia Dr. Carlos Bonorino Udaondo — CABA
• Instituto Médico de la Fundación Estudios Clínicos — Santa Fe

Brazil · 6 centers

• AC Camargo Cancer Center — São Paulo
• Fundacao PIO XII - Hospital de Amor Barretos — Barretos
• Sociedade Literaria e Caritativa Santos Agostinho - Hospital Sao José — Criciúma
• Nucleo de Pesquisa e Desenvolvimento de Medicamentos (MPDM) — Fortaleza
• Associacao Hospitalar Moinhos de Vento — Porto Alegre
• Instituto Nacional de Cancer (INCA) — Rio de Janeiro

France · 6 centers

• CHRU Tours - Hopital Trousseau — Chambray-lès-Tours
• Hopital Beaujun - APHP — Clichy
• APHM- Hopital de la Timone — Marseille
• Centre Hospitalier Universitaire Nantes — Nantes
• Centre Antoine Lacassagne — Nice
• CHU Bordeaux - Hopital Haut-Leveque — Pessac

Chile · 3 centers

• Clinical Universidad Catolica del Maule, Ltda — Maule
• Centro de Oncologia de Precision — Santiago
• CECIM-Centro de Estudios Cliicos e Investigaciones Medicas — Santiago

Italy · 3 centers

• Instituto Europeo di Oncologia — Milan
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome
• Azienda Ospedaliero Universitaria Citta Della Salute E Della Scienza Di Torino — Turin

Poland · 3 centers

• Uniwersyteckie Centrum Kliniczne im. Prof K. Gibinskiego Slaskiego Uniwersytetu Medycznego — Katowice
• Centrum Diagnostyczno-Lecznicze ,,GAMMED" — Warsaw
• Wokskowy Instytut Medyczny - Panstwowy Instytut Badawczy, Centrum Wsparcia Badań Kliniczny — Warsaw

Colombia · 2 centers

• Hospital Universitario San Ignacio — Bogotá
• Instituto Nacional de Cancerologia — Bogotá

Germany · 2 centers

• Asklepios Kilnic St. Georg — Hamburg
• Universitätsklinikum Marburg (UKGM) — Marburg

Mexico · 2 centers

• Health Pharma Professional Research S.A de C.V. — Mexico City
• Centro de Oncolégica VIVA — Mexico City

Romania · 2 centers

• Institute of Oncology Bucharest — Bucharest
• Institute of Oncology "Prof. Dr. Ion Chiricuta" Cluj Napoca — Cluj-Napoca

Identifiers

NCT: NCT07087054 · CRN00808-12 · 2024-519875-24-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗