Clinical trial NCT05797831: Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer
Official title: A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Endometrial Cancer
Keywords: navtemadlin
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: European Network of Gynaecological Oncological Trial Groups (ENGOT)
name: GOG Foundation
First posted: 2023-04-04
Enrollment: 268
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy.

The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.


Eligibility criteria: Inclusion Criteria:

* ECOG 0-1
* Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT
* Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1
* Adequate hematologic, hepatic and renal function (within 14 days)

Exclusion Criteria:

* Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation
* Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days)
* Indwelling surgical drains
* Grade 2 or higher QTc prolongation
* History of major organ transplant
* History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)

Primary outcomes:
measure: Part 1: To determine the navtemadlin Phase 3 dose
timeFrame: 12 months
measure: Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo
timeFrame: 50 months
Secondary outcomes:
measure: Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment
timeFrame: 50 months
measure: Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST)
timeFrame: 50 months
measure: Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin
timeFrame: 1 day
measure: Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin
timeFrame: 1 day
measure: Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin
timeFrame: 1 day
measure: Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR)
timeFrame: 50 months
Other outcomes:
Locations:
city: Vallejo
country: United States
facility: Kaiser Permanente Center
state: California
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Savannah
country: United States
facility: St. Joseph
state: Georgia
city: Hinsdale
country: United States
facility: Dr. Sudarshan K. Sharma, Ltd.
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Research Center
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: West Islip
country: United States
facility: Good Samaritan Hospital Medical Center
state: New York
city: Pinehurst
country: United States
facility: FirstHealth Carolinas
state: North Carolina
city: Columbus
country: United States
facility: OhioHealth Institute
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute
state: Oklahoma
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists
state: Oregon
city: Austin
country: United States
facility: Texas Oncology-Austin Central
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology-Fort Worth Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Medical Center
state: Texas
city: Graz
country: Austria
facility: University Hospital Graz, Department of Gynecology and Obstetrics
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Edmonton
country: Canada
facility: Cross Cancer Institute
city: Montreal
country: Canada
facility: CHUM - University of Montreal Hospital Centre
city: Odense
country: Denmark
facility: Odense University Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Batumi
country: Georgia
facility: LTD High Technology hospital Medcenter
city: Tbilisi
country: Georgia
facility: American Hospital Network LLC
city: Tbilisi
country: Georgia
facility: Caucasus Medical Centre
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Debrecen
country: Hungary
facility: University of Debrecen Clinical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center
city: Catania
country: Italy
facility: A.O. Cannizzaro
city: Forli
country: Italy
facility: IRCCS Istituto Romangolo per lo Studio dei Tumori "Dino Amadori"
city: Genoa
country: Italy
facility: Ospedale Policlinico San Martino
city: Lecco
country: Italy
facility: ASST di Lecco-Ospedale Alessandro Manzoni
city: Lucca
country: Italy
facility: Ospedale San Luca
city: Milan
country: Italy
facility: Osp. Niguarda
city: Parma
country: Italy
facility: University Hospital of Parma
city: Piacenza
country: Italy
facility: Ospedale Guglielmo da Saliceto
city: Prato
country: Italy
facility: Ospedale di Prato S. Stefano
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Rimini
country: Italy
facility: Azienda Unità Sanitaria Locale della Romagna - Hospital "Infermi" of Rimini Oncology Department
city: Rome
country: Italy
facility: Policlinico Umberto
city: Varese
country: Italy
facility: Ospedale Filippo Del Ponte
city: Kaunas
country: Lithuania
facility: Health Sciences Kaunas Clinics
city: Vilnius
country: Lithuania
facility: Nation Cancer Institute of Lithuania, Vilnius
city: Kristiansand
country: Norway
facility: Southern Hospital Sorlandet
city: Oslo
country: Norway
facility: Oslo University Hospital HF
city: Tromsø
country: Norway
facility: Sykehusapotek Nord Tromsø
city: Bialystok
country: Poland
facility: Białostockie Centrum Onkologii
city: Gdansk
country: Poland
facility: Szpitale Pomorskie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: NIO-PIB Oddzial w Gliwicach
city: Kraków
country: Poland
facility: Centrum Badań klinicznych Jagiellońskie Centrum Innowacji
city: Olsztyn
country: Poland
facility: Siedleckie Centrum Onkologii
city: Poznan
country: Poland
facility: Uniwersytecki Szpital
city: Warsaw
country: Poland
facility: NIO-PIB Klinika Gine-Onk
city: Wroclaw
country: Poland
facility: Lower Silesian Oncology, Pulmonology and Hematology Center, Department of Oncological Gynecology
city: Bucharest
country: Romania
facility: Bucharest CF2 Hospital
city: Constanta
country: Romania
facility: Ovidius Clinical Hospital SRL
city: Craiova
country: Romania
facility: Onco Clinic Consult S.A.
city: Craiova
country: Romania
facility: Oncology Center "Sf. Nectarie"
city: Piteşti
country: Romania
facility: Gral Medical S.R.L. - Oncofort Hospital
city: Timisoara
country: Romania
facility: Oncocenter, Oncology Clinic SRL
city: Timisoara
country: Romania
facility: SC Oncomed SRL
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
city: Maribor
country: Slovenia
facility: University Clinical Center Maribor
city: A Coruna
country: Spain
facility: CHUAC (Hospital de Coruña)
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Galdakao
country: Spain
facility: Hospital Galdakao-Usansolo
city: Jaen
country: Spain
facility: Hospital Universitario de Jaen
city: Jerez de la Frontera
country: Spain
facility: H.G.U. Jerez de la Frontera
city: Las Palmas
country: Spain
facility: Hospital U Insular de GC
city: Leon
country: Spain
facility: Hospital de Leon
city: Santiago de Compostela
country: Spain
facility: HCU Santiago de Compostela
city: Seville
country: Spain
facility: Hospital Universitario de Valme
city: Linköping
country: Sweden
facility: Linkoping University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
References: