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

Sponsor

Plexxikon (Industry)

Overall Status

Terminated

CT.gov ID

NCT01804530

Collaborator

(none)

Enrollment

Locations

Arm

53.8

Duration (Months)

14.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations Tenosynovial Giant Cell Tumor	Drug: PLX7486 TsOH	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX7486 as a Single Agent in Patients With Advanced Solid Tumors

Study Start Date :

Aug 1, 2013

Actual Primary Completion Date :

Jan 24, 2018

Actual Study Completion Date :

Jan 24, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PLX7486-TsOH, Dose escalation and RP2D Part 1: Open-label, sequential PLX7486-TsOH single-agent dose escalation in approximately 60 patients with solid tumors.	Drug: PLX7486 TsOH PLX7486 TsOH capsules, 50mg

Arm

Intervention/Treatment

Experimental: PLX7486-TsOH, Dose escalation and RP2D

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

Drug: PLX7486 TsOH

PLX7486 TsOH capsules, 50mg

Outcome Measures

Primary Outcome Measures

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] [1 year]
Area under the plasma concentration-time curve [AUC0-t, AUC0-inf] will be used to assess the pharmacokinetic profile of PLX7486.
Peak concentration (Cmax) [1 year]
Peak concentration (Cmax) will be used to assess the pharmacokinetic profile of PLX7486.
Time to peak concentration (Tmax) [1 year]
Time to peak concentration (Tmax) will be used to assess the pharmacokinetic profile of PLX7486.
Half life (t1/2) [1 year]
Half life (t1/2) will be used to assess the pharmacokinetic profile of PLX7486.
Terminal elimination rate constant (Kel) [1 year]
Terminal elimination rate constant (Kel) will be used to assess the pharmacokinetic profile of PLX7486.

Secondary Outcome Measures

Duration of response (DOR) [1 year]
Duration of response is defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first.
Progression-Free Survival (PFS) [6 month]
Progression-free survival (PFS) is defined as the number of days from start of therapy to the date of documented disease progression/relapse, whichever occurs first.
Overall Response Rate (ORR) [1year]
Overall Survival (OS) [1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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