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Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05797831
Recruitment Status : Recruiting
First Posted : April 4, 2023
Last Update Posted : April 16, 2024
Sponsor:
Collaborators:
European Network of Gynaecological Oncological Trial Groups (ENGOT)
GOG Foundation
Information provided by (Responsible Party):
Kartos Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE March 7, 2023
First Posted Date  ICMJE April 4, 2023
Last Update Posted Date April 16, 2024
Actual Study Start Date  ICMJE July 17, 2023
Estimated Primary Completion Date August 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2023)
  • Part 1: To determine the navtemadlin Phase 3 dose [ Time Frame: 12 months ]
    Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1
  • Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo [ Time Frame: 50 months ]
    PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2023)
  • Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment [ Time Frame: 50 months ]
    PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first
  • Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST) [ Time Frame: 50 months ]
    TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first
  • Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]
    Will determine the Maximum observed concentration (Cmax)
  • Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]
    Will determine the area under the plasma concentration versus time curve (AUC)
  • Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]
    Will determine the time of maximum plasma concentration (Tmax)
  • Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR) [ Time Frame: 50 months ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer
Official Title  ICMJE A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Endometrial Cancer
Intervention  ICMJE
  • Drug: Navtemadlin
    Navtemadlin is an experimental MDM2 anticancer drug taken by mouth
    Other Name: KRT-232
  • Drug: Navtemadlin Placebo
    Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth
Study Arms  ICMJE
  • Experimental: Part 1 Arm 1
    Navtemadlin administered orally at 180 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.
    Intervention: Drug: Navtemadlin
  • Experimental: Part 1 Arm 2
    Navtemadlin administered orally at 240 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.
    Intervention: Drug: Navtemadlin
  • No Intervention: Part 1 Arm 3
    Observational control ("watch and wait") on a 28-day cycle.
  • Experimental: Part 2 Arm A
    Navtemadlin administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.
    Intervention: Drug: Navtemadlin
  • Experimental: Part 2 Arm B
    Navtemadlin administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.
    Intervention: Drug: Navtemadlin
  • Placebo Comparator: Part 2 Arm C
    Placebo administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.
    Intervention: Drug: Navtemadlin Placebo
  • Placebo Comparator: Part 2 Arm D
    Placebo administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.
    Intervention: Drug: Navtemadlin Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 21, 2023)
268
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2027
Estimated Primary Completion Date August 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: John Mei 650-542-0136 jmei@kartosthera.com
Listed Location Countries  ICMJE Austria,   Denmark,   Estonia,   Finland,   Georgia,   Hungary,   Israel,   Italy,   Lithuania,   Norway,   Poland,   Romania,   Slovenia,   Spain,   Sweden,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05797831
Other Study ID Numbers  ICMJE KRT-232-118
ENGOT en-21 ( Other Identifier: ENGOT )
GOG-3089 ( Other Identifier: GOG Foundation )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Kartos Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Kartos Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • European Network of Gynaecological Oncological Trial Groups (ENGOT)
  • GOG Foundation
Investigators  ICMJE Not Provided
PRS Account Kartos Therapeutics, Inc.
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP