Clinical Trials /

PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer

NCT04493619

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Malignant Female Reproductive System Neoplasm
  • Malignant Ovarian Epithelial Tumor
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PLX2853 as a Single Agent in Advanced Gynecological Malignancies and in Combination With Carboplatin in Platinum-Resistant Epithelial Ovarian Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: PLX124-03
  • NCT ID: NCT04493619

Conditions

  • Gynecologic Neoplasms
  • Epithelial Ovarian Cancer

Interventions

DrugSynonymsArms
PLX2853PLX2853 + Carboplatin Phase 1b/2a Combination Therapy
CarboplatinPLX2853 + Carboplatin Phase 1b/2a Combination Therapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PLX2853 Phase 2a MonotherapyExperimentalUp to 26 evaluable subjects with ARID1A mutation-positive advanced gynecological malignancies will be enrolled.
  • PLX2853
PLX2853 + Carboplatin Phase 1b/2a Combination TherapyExperimentalPhase 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.
  • PLX2853
  • Carboplatin

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description: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.
Measure:Disease control rate (DCR) (both arms)
Time Frame:From time of first dose until end of treatment, an average of 6 months.
Safety Issue:
Description:DCR will be calculated as the percentage of subjects with confirmed complete response (CR), Partial Response (PR), or Stable Disease (SD).
Measure: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.
Safety Issue:
Description: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.
Measure:Overall survival (OS) (both arms)
Time Frame:From time of first dose until completion of long term follow-up, approximately 24 months.
Safety Issue:
Description: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.
Measure:PLX2853 PK parameter AUC0-last (both arms)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:AUC from time zero to time of last observed concentration hours postdose (AUC0-last).
Measure:PLX2853 PK parameter AUC0-24 (both arms)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:AUC from time zero extrapolated to 24 hours (AUC0-24)
Measure:PLX2853 PK parameter AUC0-∞ (both arms)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:AUC from time zero extrapolated to infinite time (AUC0-∞)
Measure:PLX2853 PK parameter Cmax (both arms)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:Maximum observed concentration
Measure:PLX2853 PK parameter Tmax (both arms)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:Time to maximum observed concentration
Measure:PLX2853 PK parameter T1/2 (both arms)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:terminal elimination half-life (T1/2)
Measure:PLX2853 PK parameter accumulation ratio at steady state (both arms)
Time Frame:From time of first dose until 30 days from end of treatment.
Safety Issue:
Description:accumulation ratio at steady state

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Plexxikon

Trial Keywords

  • PLX2853
  • Ovarian Cancer
  • ARID1A
  • Gynecological Malignancies
  • Carboplatin

Last Updated

July 27, 2020