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

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ClinicalTrials.gov Identifier: NCT02428712
Recruitment Status : Recruiting
First Posted : April 29, 2015
Last Update Posted : July 1, 2021
Sponsor:
Information provided by (Responsible Party):
Fore Biotherapeutics

Tracking Information
First Submitted Date  ICMJE April 20, 2015
First Posted Date  ICMJE April 29, 2015
Last Update Posted Date July 1, 2021
Study Start Date  ICMJE April 2015
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2021)
  • 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 ]
  • Maximum concentration (Cmax) of PLX8394 (Formulation 1 and Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • Time to peak concentration (Tmax) of PLX8394 (Formulation 1 and Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • Half life (T1/2) of PLX8394 (Formulation 1 and Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • Number of participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v4.0 (Formulation 1 and Formulation 2). [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • To identify the recommended Phase 2 dose (RP2D) of PLX8394 (Formulation 1) in Group A (adult patients) for further evaluation in Dose Extension. [ Time Frame: 2 years ]
  • Compare AUC of PLX8394 (Formulation 1) with PLX8394 (Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • Compare Cmax of PLX8394 (Formulation 1) with PLX8394 (Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • Compare Tmax of PLX8394 (Formulation 1) with PLX8394 (Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • Compare T1/2 of PLX8394 (Formulation 1) with PLX8394 (Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  • To determine the overall response rate of PLX8394 treatment at the applicable RP2D in a) Group A, Cohort 1, and b) Group A, Cohort 2. [ Time Frame: 5 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 23, 2015)
  • Safety of PLX8394. [ Time Frame: 1 year ]
    Safety of PLX8394 will be assessed by reported adverse events.
  • Pharmacokinetics of PLX8394 [ Time Frame: 1 year ]
    The pharmacokinetic profile of plasma PLX8394 will analyzed by measuring peak concentrations (Cmax), time to peak concentration (Tmax), and half life (t1/2).
  • Objective response [ Time Frame: 1 year ]
    Objective response as measured by the proportion of patients who achieve a complete response (CR) or partial response (PR) by RECIST 1.1.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 25, 2018)
  • 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 ]
  • 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 ]
  • Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study [ Time Frame: 5 years ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors
Official Title  ICMJE A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of PLX8394 in Patients With Advanced Unresectable Solid Tumors
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Unresectable Solid Tumors
  • BRAF-mutated Tumors
Intervention  ICMJE Drug: PLX8394
(Formulation 1 or Formulation 2)
Study Arms  ICMJE Experimental: PLX8394

Group 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
Intervention: Drug: PLX8394
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: October 13, 2020)
100
Original Estimated Enrollment  ICMJE
 (submitted: April 23, 2015)
107
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ghassan Ahmed Ghassan.Ahmed@precisionformedicine.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02428712
Other Study ID Numbers  ICMJE PLX120-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fore Biotherapeutics
Study Sponsor  ICMJE Fore Biotherapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fore Biotherapeutics
Verification Date June 2021

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