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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01804530
• Other study ID #: PLX119-01
• Status: Terminated
• Phase: Phase 1
• Start date: August 2013
• Est. completion date: January 24, 2018

Study information

• Verified date: August 2018
• Source: Plexxikon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 59
• Est. completion date: January 24, 2018
• Est. primary completion date: January 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Giant Cell Tumor of Tendon Sheath
• Giant Cell Tumors
• Neoplasms
• Solid Tumor
• Tenosynovial Giant Cell Tumor
• Tumors of Any Histology With Activating Trk (NTRK) Point or NTRK Fusion Mutations

Intervention

Drug:
• PLX7486 TsOH
PLX7486 TsOH capsules, 50mg

Locations

Country	Name	City	State
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	Ronald Reagan UCLA Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Plexxikon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of PLX7486 as single agent as measured by adverse events and serious adverse events.		1 year
Primary	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
Primary	Peak concentration (Cmax)	Peak concentration (Cmax) will be used to assess the pharmacokinetic profile of PLX7486.	1 year
Primary	Time to peak concentration (Tmax)	Time to peak concentration (Tmax) will be used to assess the pharmacokinetic profile of PLX7486.	1 year
Primary	Half life (t1/2)	Half life (t1/2) will be used to assess the pharmacokinetic profile of PLX7486.	1 year
Primary	Terminal elimination rate constant (Kel)	Terminal elimination rate constant (Kel) will be used to assess the pharmacokinetic profile of PLX7486.	1 year
Secondary	Duration of response (DOR)	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.	1 year
Secondary	Progression-Free Survival (PFS)	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.	6 month
Secondary	Overall Response Rate (ORR)		1year
Secondary	Overall Survival (OS)		1 year