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

NCT01804530 | Terminated Phase 1

• 1 other identifier: PLX119-01
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

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

Keywords

solid tumors; activating NTRK point or fusion mutations; Tenosynovial giant cell tumor; TGCT

Outcome Measures

Primary Outcomes (6)

• Safety of PLX7486 as single agent as measured by adverse events and serious adverse events.

  1 year

• Area under the plasma concentration-time curve [AUC0-t, AUC0-inf]

  Area under the plasma concentration-time curve \[AUC0-t, AUC0-inf\] will be used to assess the pharmacokinetic profile of PLX7486.

  1 year

• Peak concentration (Cmax)

  Peak concentration (Cmax) will be used to assess the pharmacokinetic profile of PLX7486.

  1 year

• Time to peak concentration (Tmax)

  Time to peak concentration (Tmax) will be used to assess the pharmacokinetic profile of PLX7486.

  1 year

• Half life (t1/2)

  Half life (t1/2) will be used to assess the pharmacokinetic profile of PLX7486.

  1 year

• Terminal elimination rate constant (Kel)

  Terminal elimination rate constant (Kel) will be used to assess the pharmacokinetic profile of PLX7486.

  1 year

Secondary Outcomes (4)

• Duration of response (DOR)

  1 year

• Progression-Free Survival (PFS)

  6 month

• Overall Response Rate (ORR)

  1year

• Overall Survival (OS)

  1 year

Study Arms (1)

PLX7486-TsOH, Dose escalation and RP2D

EXPERIMENTAL

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

Drug: PLX7486 TsOH

Interventions

PLX7486 TsOH DRUG

PLX7486 TsOH capsules, 50mg

PLX7486-TsOH, Dose escalation and RP2D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Plexxikon: lead

Study Sites (4)

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

John Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Giant Cell Tumor of Tendon Sheath

Condition Hierarchy (Ancestors)

Giant Cell Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Synovitis; Joint Diseases; Musculoskeletal Diseases; Tendinopathy; Muscular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2013
• First Posted: March 5, 2013
• Study Start: August 1, 2013
• Primary Completion: January 24, 2018
• Study Completion: January 24, 2018
• Last Updated: August 2, 2018

Record last verified: 2018-08

Locations

US (4)