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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.
See Contacts and Locations
Verified April 2017 by Plexxikon
Sponsor:
Information provided by (Responsible Party):
Plexxikon
ClinicalTrials.gov Identifier:
NCT02428712
First received: April 20, 2015
Last updated: May 2, 2017
Last verified: April 2017
  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 Drug: PLX8394 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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: May 2018
Estimated Primary Completion Date: March 2018 (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 with advanced, unresectable solid tumors.

Part 2 (not yet recruiting): Extension cohort at the R2PD of single-agent PLX8394 in approximately 65 patients with advanced cancers with an activating BRAF mutuation.

Drug: PLX8394
PLX8394 tablets, 75mg

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

  • 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02428712

Contacts
Contact: Michelle Doral Mdoral@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 Not yet recruiting
Stanford, California, United States, 94305
United States, Florida
University of Miami Not yet recruiting
Miami, Florida, United States, 33136
United States, Massachusetts
Massachusetts General Hospital Not yet recruiting
Boston, Massachusetts, United States, 02114
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
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
Study First Received: April 20, 2015
Last Updated: May 2, 2017

ClinicalTrials.gov processed this record on June 27, 2017