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

NCT ID: NCT01804530

Last Updated: 2018-08-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2018-01-24

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.

Conditions

Solid Tumor; Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations; Tenosynovial Giant Cell Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PLX7486-TsOH, Dose escalation and RP2D

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

Group Type: EXPERIMENTAL

PLX7486 TsOH

Intervention Type: DRUG

PLX7486 TsOH capsules, 50mg

Interventions

PLX7486 TsOH

PLX7486 TsOH capsules, 50mg

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Plexxikon

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

John Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

Other Identifiers

PLX119-01

Identifier Type: -

Identifier Source: org_study_id