We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian 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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04493619
Recruitment Status : Terminated (study terminated due to business realignment)
First Posted : July 30, 2020
Last Update Posted : October 5, 2022
Sponsor:
Information provided by (Responsible Party):
Opna-IO LLC

Tracking Information
First Submitted Date  ICMJE July 23, 2020
First Posted Date  ICMJE July 30, 2020
Last Update Posted Date October 5, 2022
Actual Study Start Date  ICMJE August 11, 2020
Actual Primary Completion Date April 25, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2020)
  • Phase 2a (PLX2853 monotherapy): overall response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From 8 weeks of treatment for only PLX2853 (Cycle 3 Day 1; 28 days per cycle) until completion of long term follow-up, an average of 6 months. ]
  • Phase 1b (PLX2853 + carboplatin combination): establish the MTD/RP2D for the combination of PLX2853 and carboplatin [ Time Frame: From time of first dose of PLX2853 and Carboplatin until 30 days of end of treatment. ]
  • Phase 2a (PLX2853 + carboplatin combination): ORR as measured by RECIST v1.1 [ Time Frame: From 8 weeks of treatment with PLX2853 and Carboplatin (Cycle 3 Day 1; 28 days per cycle) until completion of long term follow-up, an average of 6 months. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2020)
  • Incidence of TEAEs that are related to treatment (both arms) [ Time Frame: From time of first dose of PLX2853 and Carboplatin until 30 days of end of treatment. ]
  • Incidence of TEAEs that result in dose interruption, reduction or discontinuation (both arms) [ Time Frame: From time of first dose of PLX2853 and Carboplatin until 30 days of end of treatment. ]
  • Incidence of treatment-emergent ECG abnormalities (both arms) [ Time Frame: From time of first dose of PLX2853 and Carboplatin until 30 days of end of treatment. ]
  • Incidence of treatment-emergent laboratory abnormalities (both arms) [ Time Frame: From time of first dose of PLX2853 and Carboplatin until 30 days of end of treatment. ]
  • Duration Of Response (DOR) (both arms) [ Time Frame: From 8 weeks of treatment (Cycle 3 Day 1; 28 days per cycle) until completion of long term follow-up, an average of 6 months. ]
    DOR will be calculated for each subject with a response as the number of days from the date of first response (PR or CR confirmed at least 28 days later) to the date of the first documented disease progression or date of death from any cause, whichever occurs first.
  • Disease control rate (DCR) (both arms) [ Time Frame: From time of first dose until end of treatment, an average of 6 months. ]
    DCR will be calculated as the percentage of subjects with confirmed complete response (CR), Partial Response (PR), or Stable Disease (SD).
  • Progression-free survival (PFS) (both arms) [ Time Frame: From time of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 24 months. ]
    Progression-free survival (PFS) will be calculated for each subject as the number of days from the first day of PLX2853 treatment (Cycle 1 Day 1) to the date of the first documented disease progression or date of death from any cause, whichever occurs first.
  • Overall survival (OS) (both arms) [ Time Frame: From time of first dose until completion of long term follow-up, approximately 24 months. ]
    Overall survival (OS) will be calculated for each subject as the number of days from the first day of PLX2853 treatment (Cycle 1 Day 1) to the date of death from any cause.
  • PLX2853 PK parameter AUC0-last (both arms) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    AUC from time zero to time of last observed concentration hours postdose (AUC0-last).
  • PLX2853 PK parameter AUC0-24 (both arms) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    AUC from time zero extrapolated to 24 hours (AUC0-24)
  • PLX2853 PK parameter AUC0-∞ (both arms) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    AUC from time zero extrapolated to infinite time (AUC0-∞)
  • PLX2853 PK parameter Cmax (both arms) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    Maximum observed concentration
  • PLX2853 PK parameter Tmax (both arms) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    Time to maximum observed concentration
  • PLX2853 PK parameter T1/2 (both arms) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    terminal elimination half-life (T1/2)
  • PLX2853 PK parameter accumulation ratio at steady state (both arms) [ Time Frame: From time of first dose until 30 days from end of treatment. ]
    accumulation ratio at steady state
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 PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer
Official Title  ICMJE A Multicenter, Open-Label, Parallel, Phase 2a Study of PLX2853 Monotherapy in Advanced Gynecological Malignancies With a Known ARID1A Mutation and Phase 1b/2a Study of PLX2853/Carboplatin Combination Therapy in Platinum-Resistant Epithelial Ovarian Cancer
Brief Summary The purpose of this research study is to evaluate safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the investigational drug PLX2853 in Advanced Gynecological Malignancies with a Known ARID1A Mutation and PLX2853/Carboplatin Combination Therapy in Platinum-Resistant Epithelial Ovarian Cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gynecologic Neoplasms
  • Epithelial Ovarian Cancer
Intervention  ICMJE
  • Drug: PLX2853
    PLX2853 tablets
  • Drug: Carboplatin
    Carboplatin IV injection, 5 mg•min/mL
Study Arms  ICMJE
  • Experimental: PLX2853 Phase 2a Monotherapy
    Up to 26 evaluable subjects with ARID1A mutation-positive advanced gynecological malignancies will be enrolled.
    Intervention: Drug: PLX2853
  • Experimental: PLX2853 + Carboplatin Phase 1b/2a Combination Therapy

    Phase 1b (PLX2853 + carboplatin combination): Up to 15 evaluable subjects with platinum-resistant EOC will be enrolled.

    Phase 2a (PLX2853 + carboplatin combination): Up to 26 evaluable subjects with platinum-resistant EOC will be enrolled.

    Interventions:
    • Drug: PLX2853
    • Drug: Carboplatin
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 Terminated
Actual Enrollment  ICMJE
 (submitted: July 19, 2022)
37
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2020)
67
Actual Study Completion Date  ICMJE April 25, 2022
Actual Primary Completion Date April 25, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age ≥18 years at the time of signing informed consent
  2. Histologically or cytologically confirmed diagnosis of 1 of the following, and must have measurable disease per RECIST v1.1:

    • Phase 2a (PLX2853 monotherapy): Any advanced gynecological malignancy (cervical, vaginal, vulvar, uterine, ovarian, fallopian tube, or primary peritoneal) with a known ARID1A mutation, that is intolerant to or refractory to all standard therapy known to confer clinical benefit.
    • Phase 1b and Phase 2a (PLX2853 + carboplatin combination):

    Platinum-resistant EOC (including fallopian tube or primary peritoneal cancer).

  3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
  4. Adequate organ function as demonstrated by laboratory values.
  5. Women of child bearing potential (defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal) must have a negative serum pregnancy test within 7 days prior to taking the first dose of study drug and, if sexually active, must agree to use a highly effective method of contraception (a contraception method with a failure rate <1% per year) and 1 additional barrier method from the time of the negative pregnancy test to 90 days after the last dose of study drug. Women of non-child bearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year.
  6. Except as specified above for organ function, all drug-related toxicity from previous cancer therapy must be resolved (to Grade ≤1 or baseline per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 [NCI CTCAE v5.0]) prior to study treatment administration (Grade 2: alopecia, hot flashes, decreased libido, or neuropathy is allowed).
  7. Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements

Exclusion Criteria:

  1. Prior exposure to a bromodomain inhibitor
  2. Ongoing systemic infection requiring treatment with antibiotic, antiviral, or antifungal treatment
  3. Autoimmune hemolytic anemia or autoimmune thrombocytopenia
  4. Presence of symptomatic or uncontrolled central nervous system or leptomeningeal metastases
  5. Red blood cell or platelet transfusion within 14 days of Screening blood draw
  6. Known or suspected allergy to the investigational agent or any agent given in association with this study
  7. Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 μg (NIH-ODS 2020).
  8. Use of strong inhibitors and inducers of CYP3A4 and 2C8
  9. Clinically significant cardiac disease
  10. Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
  11. Non-healing wound, ulcer, or bone fracture
  12. Infection with HIV-1 or HIV-2. Exception: subjects with well-controlled HIV (e.g., CD4 >350/mm3 and undetectable viral load) are eligible.
  13. Current active liver disease from any cause, including hepatitis A (hepatitis A virus immunoglobulin M positive), hepatitis B (hepatitis B virus [HBV] surface antigen positive), or hepatitis C (hepatitis C virus [HCV] antibody positive, confirmed by HCV ribonucleic acid).
  14. Active known second malignancy with the exception of any of the following:

    • Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer
    • Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years
    • Any other cancer from which the subject has been disease-free for ≥3 years
  15. Major surgery or significant traumatic injury within 28 days prior to Cycle 1 Day 1
  16. Hospitalization for subacute bowel obstruction within 28 days prior to Cycle 1 Day 1
  17. Receipt of anti-cancer therapy prior to Cycle 1 Day 1:

    • Chemotherapy, radiation therapy, or small molecule anti-cancer therapy for the treatment of cancer within 14 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1
    • Immune therapy or other biologic therapy (e.g., monoclonal antibodies, antibody-drug conjugates) for the treatment of cancer within 21 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1 Subjects can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 28 days prior to treatment with study drug.
  18. Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed).
  19. Subjects who are pregnant or breast-feeding
  20. Presence of any other medical, psychological, familial, sociological, or geographic condition potentially hampering compliance with the study protocol or would interfere with the study endpoints or the subject's ability to participate.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04493619
Other Study ID Numbers  ICMJE PLX124-03
Has Data Monitoring Committee No
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 Opna-IO LLC
Original Responsible Party Plexxikon
Current Study Sponsor  ICMJE Opna-IO LLC
Original Study Sponsor  ICMJE Plexxikon
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Opna-IO LLC
Verification Date October 2022

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