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Trial record 1 of 1 for:    NCT02428712
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A Study of PLX8394 as a Single Agent in Patients With Advanced Unresectable Solid Tumors

This study is currently recruiting participants.
Verified October 2017 by Plexxikon
Sponsor:
ClinicalTrials.gov Identifier:
NCT02428712
First Posted: April 29, 2015
Last Update Posted: October 26, 2017
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.
Information provided by (Responsible Party):
Plexxikon
  Purpose
The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of PLX8394.

Condition Intervention Phase
Advanced Unresectable Solid Tumors BRAF-mutated Tumors Drug: PLX8394 Phase 1 Phase 2

Study Type: Interventional
Study Design: 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

Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • To evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered PLX8394 in patients with advanced solid tumors [Part 1] [ Time Frame: 1 year ]
  • To identify the recommended Phase 2 dose (RP2D) of PLX8394 [Part 1] [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • To assess objective tumor response in patients with advanced BRAF-mutated cancers treated with PLX8394. [Part 2] [ Time Frame: 1 year ]
  • To assess response rate by Response Evaluation Criteria in Solid Tumors [Part 2] [ Time Frame: 1 year ]
  • To assess the PK, PD, and safety of PLX8394 [Part 2] [ Time Frame: 1 year ]

Estimated Enrollment: 107
Study Start Date: April 2015
Estimated Study Completion Date: July 2020
Estimated Primary Completion Date: April 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PLX8394

Part 1: Open-label, sequential, PLX8394 single-agent dose escalation in approximately 42 patients (adults- Group A and pediatrics- Group B) with advanced, unresectable solid tumors.

Part 2: Extension cohort at the R2PD of single-agent PLX8394 in approximately 65 patients (adults- Group A and pediatrics- Group B) with advanced cancers with an activating BRAF mutuation.

Drug: PLX8394
PLX8394 tablets, 75mg

Detailed Description:

Dose Escalation (Part 1): To evaluate safety, pharmacokinetics, pharmacodynamics of PLX8394 in adults and pediatrics 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 adults and in pediatric patients with advanced BRAF- mutated tumors, to access RECIST, and to access pharmacokinetics, pharmacodynamics, and safety.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria- Group A:

  • Age ≥ 18 years.
  • Dose-escalation Cohorts: Patients with advanced solid tumors who are refractory to, relapsed after or intolerant to standard therapy, or for whom no standard therapy exists.
  • Extension Cohorts: Patients with a history of solid tumors with an activating BRAF mutation

    1. Melanoma: Patients with unresectable Stage IIIC or Stage IV disease; Refractory to, relapsed after, or intolerant to treatment with (a) a BRAF or BRAF/MEK inhibitor and/or (b) FDA-approved immunotherapy
    2. Non-melanoma solid tumors:

      1. No prior exposure to RAS/RAF/MEK/ERK pathway inhibitors
      2. Patients who are refractory to, relapsed after or intolerant to standard therapy, or for whom no standard therapy exists: (i) Advanced thyroid carcinoma -- Anaplastic thyroid carcinoma: Positive (IHC) for V600E (or known history of BRAF mutation) is allowed to enroll; Locoregional disease no longer amenable to curative surgery or radiation, or advanced disease with measurable primary or metastatic disease; Papillary thyroid carcinoma -- Must be beyond 3 weeks from last radioactive iodine treatment and AEs associated with previous therapy must be resolved to Grade 1 or baseline; Thyroid stimulating hormone (TSH) less than the upper limit of normal (ULN) per institutional laboratory ranges. (ii) Other advanced tumors (eg. colorectal cancer, non-small cell lung cancer, cholangiocarcinoma.
  • Measurable disease by RECIST 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Adequate hematologic, hepatic, and renal function.
  • Women of child-bearing potential must have a negative serum pregnancy at Screening 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. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. 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 (e.g. chemotherapy, immunotherapy, tyrosine kinase inhibitor, or radiation therapy) at least 2 weeks before study drug initiation, with resolution of all associated toxicity (to ≤ Grade 1 or Baseline) prior to PLX8394 administration.
  • Willingness and ability to provide written informed consent prior to any study-related procedures and to comply with all study requirements.

Exclusion Criteria- Group A:

  • Symptomatic brain metastases. Patients with untreated brain metastasis ≤ 1 cm can be considered eligible if deemed asymptomatic by the investigator upon consultation with the Medical Monitor and do not require immediate radiation or steroids. Patients with brain metastasis that is treated and stable for 1 month may be considered eligible if they are asymptomatic and on stable dose (>2 weeks) of steroids or if they do not require steroids following successful local therapy.
  • Dose-escalation Cohorts: Investigational drug use within 28 days (or 5 half-lives, whichever is longer) of the first dose of PLX8394
  • Extension Cohorts: 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 (unless the wound has healed), or anticipation of the need for major surgery during the study.
  • Uncontrolled intercurrent illness.
  • Active secondary malignancy unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor. Examples of the latter include basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, and isolated elevation of prostate-specific antigen. 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.
  • Baseline mean QT interval corrected using Fridericia's equation (QTcF) ≥ 450 msec (males) or ≥ 470 msec (females).
  • Clinically significant cardiac arrhythmias including bradyarrhythmias and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
  • Congenital long QT syndrome or patients taking concomitant medications known to prolong the QT interval (e.g., tricyclics, azithromycin, methadome).
  • History of clinically significant cardiac disease or congestive heart failure >New York Heart Association (NYHA) class 2. Patient must not have unstable angina (angina symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.
  • Women who are breast-feeding or pregnant.
  • Known chronic human immunodeficiency virus (HIV), Hepatitis C virus (HCV), or Hepatitis B virus (HBV) infection.
  • Imprisonment or under legal guardianship.
  • The presence of a medical or psychiatric condition that, in the opinion of the investigator, makes the patient inappropriate for study inclusion.
  • Inability to swallow and retain study drug.

Inclusion Criteria — Group B:

  • Minimum developmental age: the ability to swallow and retain study drug and a minimum body surface area (BSA) that allows a PLX8394 dose level of at least 75 mg BID.
  • Patients with a history of activating BRAF mutation, including the following:

A. Diagnosis of pediatric brain tumor (e.g., pilocytic astrocytoma, pleomorphic xanthoastrocytoma, ganglioglioma, astrocytoma, papillary craniopharyngioma, glioblastoma) with an activating BRAF mutation.

B. Histologically proven LCH with an activating BRAF mutation. C. Diagnosis of LCH-associated neurodegenerative disease (LCH-ND) with an activating BRAF mutation in tumor biopsy or in circulating cells and radiologic progression within the past 3 months or radiologic evidence of neurodegeneration with an ataxia rating score >20.

D. Other advanced malignancy with an activating BRAF mutation.

• The following previous therapy experience: A. Pediatric brain tumors with measurable disease — failure of front-line therapy.

B. High-risk LCH with measurable disease — failure of front-line therapy. C. Low-risk LCH with measurable disease — failure of second-line therapy. D. LCH-ND — no previous therapy required. E. Other measurable solid tumors (e.g., melanoma, Wilm's tumor, papillary thyroid carcinoma) refractory to, relapsed after, or intolerant to standard therapy or for whom no standard therapy exists.

  • ECOG performance status of 0-2.
  • Adequate hematologic, hepatic, and renal function.
  • .Females of child-bearing potential must have a negative serum pregnancy at within 7 days prior to Cycle 1 Day 1 and must agree to use an effective form of contraception from the time of the negative pregnancy test and for 3 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Females of non-child-bearing potential may be included if they are either surgically sterile, have been postmenopausal for ≥1 year, or are premenopausal.
  • Fertile male patients must agree to use an effective method of birth control during the study and for 3 months after the last dose of study drug.
  • Completion of previous chemotherapy, immunotherapy, or targeted therapy (including MAPK pathway inhibitors) at least 1 month (or 5 half-lives, whichever is longer) before study drug initiation, with resolution of all associated toxicity prior to PLX8394 administration.
  • .All patients or their legal guardians (if the patient is <18 years old) must sign an IRB-approved document of informed consent to demonstrate their understanding of the investigational nature and the risks of this study before any protocol-related procedures are performed. When appropriate, pediatric subjects will be included in all discussions.

Exclusion Criteria — Group B:

  • Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating the study drug (unless the wound has healed), or anticipation of the need for major surgery during the study.
  • Dose Escalation — Investigational drug use within 28 days (or 5 half-lives, whichever is longer) of the first dose of PLX8394.
  • Dose Extension — Investigational drug use within 28 days (or 5 half-lives, whichever is shorter) of the first dose of PLX8394.
  • Uncontrolled intercurrent illness.
  • Active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety and is approved by the Medical Monitor.
  • Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption.
  • Patients with >Grade 1 (high or low) serum potassium, magnesium, or calcium levels.
  • Baseline QTcF interval >450 msec (males) or >470 msec (females).
  • Patients with clinically significant cardiac arrhythmias, including brady-arrhythmias, and/or patients who require anti-arrhythmic therapy (excluding beta blockers or digoxin). Patients with controlled atrial fibrillation are not excluded.
  • Patients with congenital long QT syndrome or patients taking concomitant mediations known to prolong the QT interval.
  • History of clinically significant cardiac disease or congestive heart failure >NYHA class 2. Patients must not have unstable angina or new-onset angina within the last 3 months or myocardial infarction within the past 6 months.
  • Females who are breast-feeding or pregnant.
  • Known chronic HIV, HCV, or HBV infection.
  • The presence of a medical or psychiatric condition that, in the opinion of the investigator, makes the patient inappropriate for study inclusion.
  Contacts and Locations
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
Contact: Terry Cho tcho@plexxikon.com

Locations
United States, Arizona
HonorHealth Recruiting
Scottsdale, Arizona, United States, 85258
United States, California
University of California, San Francisco Not yet recruiting
San Francisco, California, United States, 94143
Stanford Hospitals and Clinics Recruiting
Stanford, California, United States, 94305
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
United States, Pennsylvania
Thomas Jefferson University Medical Oncology Clinica Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Vanderbilt University Not yet recruiting
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) Not yet recruiting
Houston, Texas, United States, 77030
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Plexxikon
  More Information

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT02428712     History of Changes
Other Study ID Numbers: PLX120-03
First Submitted: April 20, 2015
First Posted: April 29, 2015
Last Update Posted: October 26, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Neoplasms