Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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: NCT02428712
Recruitment Status : Recruiting
First Posted : April 29, 2015
Last Update Posted : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
NovellusDx

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

Condition or disease Intervention/treatment Phase
Advanced Unresectable Solid Tumors BRAF-mutated Tumors Drug: PLX8394 Phase 1 Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of PLX8394 in Patients With Advanced Unresectable Solid Tumors
Study Start Date : April 2015
Estimated Primary Completion Date : February 2022
Estimated Study Completion Date : June 2022

Arm Intervention/treatment
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

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.

Drug: PLX8394
(Formulation 1 or Formulation 2)




Primary Outcome Measures :
  1. 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 ]
  2. Maximum concentration (Cmax) of PLX8394 (Formulation 1 and Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. To identify the RP2D of PLX8394 (Formulation 1) in Group B (pediatric patients) for further evaluation in Dose Extension. [ Time Frame: 1 year ]
  8. Compare AUC of PLX8394 (Formulation 1) with PLX8394 (Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  9. Compare Cmax of PLX8394 (Formulation 1) with PLX8394 (Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  10. Compare Tmax of PLX8394 (Formulation 1) with PLX8394 (Formulation 2) [ Time Frame: First dose of PLX8394 up to 30 days after end of treatment ]
  11. 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 ]
  12. To determine the overall response rate of PLX8394 treatment at the applicable RP2D in a) Group A, Cohort 1, b) Group A, Cohort 2, and c) Group B. [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Clinical benefit rate (defined as stable disease, partial response and complete response) after 24 weeks on study [ Time Frame: 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02428712


Contacts
Layout table for location contacts
Contact: Ghassan Ahmed Ghassan.Ahmed@precisionformedicine.com

Locations
Layout table for location information
United States, Arizona
HonorHealth Recruiting
Scottsdale, Arizona, United States, 85258
United States, California
University of California, San Francisco Withdrawn
San Francisco, California, United States, 94143
Stanford Hospitals and Clinics Completed
Stanford, California, United States, 94305
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
United States, Massachusetts
Massachusetts General Hospital Active, not recruiting
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center Withdrawn
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute Completed
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Thomas Jefferson University Medical Oncology Clinica Withdrawn
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Vanderbilt University Withdrawn
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Texas Children's Hospital (Baylor College of Medicine) Recruiting
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute Completed
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
NovellusDx
Layout table for additonal information
Responsible Party: NovellusDx
ClinicalTrials.gov Identifier: NCT02428712    
Other Study ID Numbers: PLX120-03
First Posted: April 29, 2015    Key Record Dates
Last Update Posted: November 5, 2020
Last Verified: October 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms