Endometrial Cancer Clinical Trial
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
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.
| Status | Recruiting |
| Enrollment | 268 |
| Est. completion date | July 2027 |
| Est. primary completion date | August 2025 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| Austria | University Hospital Graz, Department of Gynecology and Obstetrics | Graz | |
| Austria | Medizinische Universität Innsbruck | Innsbruck | |
| Austria | Medizinische Universität Wien | Vienna | |
| Canada | Cross Cancer Institute | Edmonton | |
| Canada | CHUM - University of Montreal Hospital Centre | Montreal | |
| Denmark | Odense University Hospital | Odense | |
| Estonia | Tartu University Hospital | Tartu | |
| Finland | Kuopio University Hospital | Kuopio | |
| Finland | Turku University Hospital | Turku | |
| Georgia | LTD High Technology hospital Medcenter | Batumi | |
| Georgia | American Hospital Network LLC | Tbilisi | |
| Georgia | Caucasus Medical Centre | Tbilisi | |
| Hungary | National Institute of Oncology | Budapest | |
| Hungary | University of Debrecen Clinical Center | Debrecen | |
| Israel | Rambam Medical Center | Haifa | |
| Israel | Shaare Zedek Medical Center | Jerusalem | |
| Israel | Sourasky Medical Center | Tel-Aviv | |
| Italy | A.O. Cannizzaro | Catania | |
| Italy | IRCCS Istituto Romangolo per lo Studio dei Tumori "Dino Amadori" | Forli | |
| Italy | Ospedale Policlinico San Martino | Genoa | |
| Italy | ASST di Lecco-Ospedale Alessandro Manzoni | Lecco | |
| Italy | Ospedale San Luca | Lucca | |
| Italy | Osp. Niguarda | Milan | |
| Italy | University Hospital of Parma | Parma | |
| Italy | Ospedale Guglielmo da Saliceto | Piacenza | |
| Italy | Ospedale di Prato S. Stefano | Prato | |
| Italy | Ospedale Santa Maria delle Croci | Ravenna | |
| Italy | "Azienda Unità Sanitaria Locale della Romagna - Hospital ""Infermi"" of Rimini Oncology Department" | Rimini | |
| Italy | Policlinico Umberto | Rome | |
| Italy | Ospedale Filippo Del Ponte | Varese | |
| Lithuania | Health Sciences Kaunas Clinics | Kaunas | |
| Lithuania | Nation Cancer Institute of Lithuania, Vilnius | Vilnius | |
| Norway | Southern Hospital Sorlandet | Kristiansand | |
| Norway | Oslo University Hospital HF | Oslo | |
| Norway | Sykehusapotek Nord Tromsø | Tromsø | |
| Poland | Bialostockie Centrum Onkologii | Bialystok | |
| Poland | Szpitale Pomorskie | Gdansk | |
| Poland | Uniwersyteckie Centrum Kliniczne | Gdansk | |
| Poland | NIO-PIB Oddzial w Gliwicach | Gliwice | |
| Poland | Centrum Badan klinicznych Jagiellonskie Centrum Innowacji | Kraków | |
| Poland | Siedleckie Centrum Onkologii | Olsztyn | |
| Poland | Uniwersytecki Szpital | Poznan | |
| Poland | NIO-PIB Klinika Gine-Onk | Warsaw | |
| Poland | Lower Silesian Oncology, Pulmonology and Hematology Center, Department of Oncological Gynecology | Wroclaw | |
| Romania | Bucharest CF2 Hospital | Bucharest | |
| Romania | Ovidius Clinical Hospital SRL | Constanta | |
| Romania | Onco Clinic Consult S.A. | Craiova | |
| Romania | Oncology Center "Sf. Nectarie" | Craiova | |
| Romania | Gral Medical S.R.L. - Oncofort Hospital | Pitesti | |
| Romania | Oncocenter, Oncology Clinic SRL | Timisoara | |
| Romania | SC Oncomed SRL | Timisoara | |
| Slovenia | Institute of Oncology Ljubljana | Ljubljana | |
| Slovenia | University Clinical Center Maribor | Maribor | |
| Spain | CHUAC (Hospital de Coruña) | A Coruna | |
| Spain | Hospital del Mar | Barcelona | |
| Spain | Hospital Galdakao-Usansolo | Galdakao | |
| Spain | Hospital Universitario de Jaen | Jaen | |
| Spain | H.G.U. Jerez de la Frontera | Jerez de la Frontera | |
| Spain | Hospital U Insular de GC | Las Palmas | |
| Spain | Hospital de Leon | Leon | |
| Spain | HCU Santiago de Compostela | Santiago de Compostela | |
| Spain | Hospital Universitario de Valme | Seville | |
| Sweden | Linkoping University Hospital | Linköping | |
| Sweden | Karolinska University Hospital | Stockholm | |
| United States | Northside Hospital | Atlanta | Georgia |
| United States | Texas Oncology-Austin Central | Austin | Texas |
| United States | OhioHealth Institute | Columbus | Ohio |
| United States | Oncology Associates of Oregon | Eugene | Oregon |
| United States | Parkview Research Center | Fort Wayne | Indiana |
| United States | Texas Oncology-Fort Worth Cancer Center | Fort Worth | Texas |
| United States | Dr. Sudarshan K. Sharma, Ltd. | Hinsdale | Illinois |
| United States | Indiana University | Indianapolis | Indiana |
| United States | Women's Cancer Center of Nevada | Las Vegas | Nevada |
| United States | Minnesota Oncology Hematology, P.A. | Minneapolis | Minnesota |
| United States | FirstHealth Carolinas | Pinehurst | North Carolina |
| United States | Northwest Cancer Specialists | Portland | Oregon |
| United States | Washington University School of Medicine | Saint Louis | Missouri |
| United States | Texas Oncology-San Antonio Medical Center | San Antonio | Texas |
| United States | St. Joseph | Savannah | Georgia |
| United States | Maryland Oncology Hematology, P.A. | Silver Spring | Maryland |
| United States | Oklahoma Cancer Specialists and Research Institute | Tulsa | Oklahoma |
| United States | Kaiser Permanente Center | Vallejo | California |
| United States | Good Samaritan Hospital Medical Center | West Islip | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Kartos Therapeutics, Inc. | European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation |
United States, Austria, Canada, Denmark, Estonia, Finland, Georgia, Hungary, Israel, Italy, Lithuania, Norway, Poland, Romania, Slovenia, Spain, Sweden,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Part 1: To determine the navtemadlin Phase 3 dose | Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1 | 12 months | |
| Primary | Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo | PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first | 50 months | |
| Secondary | Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment | PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first | 50 months | |
| Secondary | Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST) | TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first | 50 months | |
| Secondary | Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin | Will determine the Maximum observed concentration (Cmax) | 1 day | |
| Secondary | Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin | Will determine the area under the plasma concentration versus time curve (AUC) | 1 day | |
| Secondary | Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin | Will determine the time of maximum plasma concentration (Tmax) | 1 day | |
| Secondary | Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR) | Best response of complete response (CR), partial response (PR) or stable disease (SD) by IRC/investigator assessment among subjects with PR as best response from prior chemotherapy | 50 months |
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