Status:

TERMINATED

Phase 1 Study of PLX7486 as Single Agent in Patients With Advanced Solid Tumors

Lead Sponsor:

Plexxikon

Conditions:

Solid Tumor

Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations

Eligibility:

All Genders

18+ years

Phase:

PHASE1

Brief Summary

The objective of this study is to determine the safety, pharmacokinetics, maximum tolerated dose/recommended Phase 2 dose, and efficacy of PLX7486.

Detailed Description

Part 1. Open-label, sequential PLX7486 TsOH single-agent dose escalation in approximately 60 patients with solid tumors.

Eligibility Criteria

Inclusion

  • Inclusion Criteria
  • Male or female ≥18 years old
  • Patients with histologically confirmed solid tumors who:
  • o Part 1: have tumor progression following standard therapy, have treatment-refractory disease, or for whom there is no effective standard of therapy
  • Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use an acceptable method of birth control. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for ≥1 year. Fertile men must also agree to use an acceptable method of birth control while on study drug and up to 3 months after the last dose of study drug.
  • All associated toxicity from previous or concurrent cancer therapy must be resolved (to ≤Grade 1 or Baseline) prior to study treatment administration
  • Patients with stable, treated brain metastases are eligible for this trial. However, patients must not have required steroid treatment for their brain metastases within 30 days of Screening.
  • Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements
  • Karnofsky performance status ≥70%
  • Life expectancy ≥3 months
  • Adequate hematologic, hepatic, and renal function
  • Exclusion Criteria
  • Other than the primary malignancy, active cancer (either concurrent or within the last 3 years) that requires non-surgical therapy (e.g., chemotherapy or radiation therapy), with the exception of surgically treated basal or squamous cell carcinoma of the skin, melanoma in situ, or carcinoma in-situ of the cervix
  • Chemotherapy within 28 days prior to C1D1
  • Biological therapy within 5 half-lives prior to C1D1
  • Radiation therapy within 28 days or 5 half-lives prior to C1D1, whichever is longer
  • Investigational drug use within 28 days or 5 half-lives, whichever is longer, prior to C1D1
  • Part 1 only: (a) Patients with active or a history of glucose intolerance or diabetes mellitus and (b) Hemoglobin A1c ≥7%
  • ≥Grade 2 sensory neuropathy at baseline
  • Uncontrolled intercurrent illness (i.e., active infection) or concurrent condition that, in the opinion of the Investigator, would interfere with the study endpoints or the patient's ability to participate
  • Refractory nausea and vomiting, malabsorption, small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
  • Mean QTcF ≥450 msec (for males) or ≥470 msec (for females) at Screening
  • The presence of a medical or psychiatric condition that, in the opinion of the Principal Investigator, makes the patient inappropriate for inclusion in this study

Exclusion

    Key Trial Info

    Start Date :

    August 1 2013

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    January 24 2018

    Estimated Enrollment :

    59 Patients enrolled

    Trial Details

    Trial ID

    NCT01804530

    Start Date

    August 1 2013

    End Date

    January 24 2018

    Last Update

    August 2 2018

    Active Locations (4)

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    Page 1 of 1 (4 locations)

    1

    Ronald Reagan UCLA Medical Center

    Los Angeles, California, United States, 90095

    2

    John Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, United States, 21231

    3

    Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, United States, 02114

    4

    Medical University of South Carolina

    Charleston, South Carolina, United States, 29425