Clinical Trials /

A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors

NCT02428712

Description:

The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of PLX8394.

Related Conditions:
  • Glioma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors
  • Official Title: A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of PLX8394 in Patients With Advanced Unresectable Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: PLX120-03
  • NCT ID: NCT02428712

Conditions

  • Advanced Unresectable Solid Tumors
  • BRAF-mutated Tumors

Interventions

DrugSynonymsArms
PLX8394PLX8394

Purpose

The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of PLX8394.

Detailed Description

      Dose Escalation (Part 1): To evaluate safety, pharmacokinetics, pharmacodynamics of PLX8394
      in adult and pediatric patients with advanced BRAF- mutated tumors, and to identify the
      recommended Phase 2 Dose.

      Dose Extension (Part 2): To access objective tumor response to PLX8394 treatment in adult and
      in adolescent patients with advanced BRAF- mutated tumors, to access RECIST, and to access
      pharmacokinetics, pharmacodynamics, and safety.
    

Trial Arms

NameTypeDescriptionInterventions
PLX8394ExperimentalGroup A: Phase 1-Dose Escalation: Adult patients. Phase 2a-RP2D Confirmation/Redefinition (Formulation 2): Adult and adolescent patients. Phase 2a-Dose Extension: Adult and adolescent patients with advanced unresectable solid tumors will be enrolled among two cohorts. Cohort 1: Activating BRAF V600 mutations (glioma patients only) Cohort 2: Activating BRAF non-V600 mutations Group B: Phase 1-Dose Escalation: Pediatric patients. Enrollment to Group B is closed. Phase 2a-Dose Extension: Pediatric patients with advanced unresectable BRAF-mutated tumors, including LCH. As of Protocol Amendment 10, enrollment to Group B is closed.
  • PLX8394

Eligibility Criteria

        Inclusion Criteria- Group A:

          -  Age ≥ 12 years and at least 40 kg.

          -  Phase 1-Dose Escalation (no longer enrolling as of Protocol Amendment 10): Patients
             with histologically confirmed advanced solid tumors who are refractory to, relapsed
             after, or intolerant to standard therapy or for whom no standard therapy exists.

          -  Phase 2a-RP2D Confirmation/Redefinition (Formulation 2) and Phase 2a-Dose Extension:
             Patients with a history of histologically confirmed solid tumors with a BRAF mutation.
             Following RP2D confirmation and redefinition, extension subjects must meet criteria
             for Cohort 1 and Cohort 2 as specified below:

               -  Phase 2a-Dose Extension-Cohort 1

                    1. Patients with solid tumors (as of Amendment 10, only subjects with glioma
                       tumors) driven by a BRAF-V600 mutation

                    2. Patients with no prior exposure to BRAF-directed therapy and for whom no
                       standard therapy exists.

               -  Phase 2a-Dose Extension-Cohort 2

                    1. Patients with solid tumors driven by BRAF non-V600 mutation.

                    2. Patients with prior exposure to BRAF-directed therapy will be allowed,
                       pending confirmation of mutations in either a re-biopsy or ctDNA, if the
                       mutational profile identifies a potential for response based on PLX8394
                       mechanism of action and after investigator discussion.

          -  Measurable disease by RECIST 1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          -  Adequate hematologic, hepatic, and renal function.

          -  Women of child-bearing potential must have a negative pregnancy test and must agree to
             use an effective form of contraception from the time of the negative pregnancy test up
             to 3 months 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.

          -  Fertile men must agree to use an effective method of birth control during the study
             and for up to 3 months after the last dose of study drug.

          -  Completion of previous anti-cancer therapy at least 2 weeks before study drug
             initiation.

        Exclusion Criteria- Group A:

          -  Phase 1 and Phase 2a RP2D confirmation-Dose Escalation: Investigational drug use
             within 28 days (or 5 half-lives, whichever is shorter) of the first dose of PLX8394.

          -  Major surgical procedure, open biopsy (excluding skin cancer resection), or
             significant traumatic injury within 14 days of initiating study drug or anticipation
             of the need for major surgery during the study.

          -  Uncontrolled intercurrent illness.

          -  Patients with colorectal cancer or pancreatic cancer

          -  Active secondary malignancy unless the malignancy is not expected to interfere with
             the evaluation of safety and is approved by the Medical Monitor. Patients with a
             completely treated prior malignancy and no evidence of disease for ≥ 2 years are
             eligible.

          -  Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
             bowel resection that would preclude adequate absorption.

          -  Clinically significant cardiac disease.

          -  Known infection with HIV, HBV, or HCV or a known carrier of HBV or HCV.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Area under the curve (AUC) of PLX8394 (Formulation 1 and Formulation 2)
Time Frame:First dose of PLX8394 up to 30 days after end of treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To evaluate the duration of response (defined as time of initial response to progressive disease or death) at the applicable RP2D in Dose Extension.
Time Frame:5 years
Safety Issue:
Description:
Measure:To evaluate the progression free survival (defined as time of first dose to progressive disease or death) at the applicable RP2D in Dose Extension.
Time Frame:5 years
Safety Issue:
Description:
Measure:Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study
Time Frame:5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NovellusDx

Last Updated

November 5, 2020