Clinical trial NCT01804530: Phase 1 Study of PLX7486 as Single Agent in Patients With Advanced Solid Tumors
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Plexxikon
Sponsor class: INDUSTRY
First posted: 2013-03-05
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 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

Primary outcomes:
measure: Safety of PLX7486 as single agent as measured by adverse events and serious adverse events.
timeFrame: 1 year
measure: Area under the plasma concentration-time curve [AUC0-t, AUC0-inf]
timeFrame: 1 year
measure: Peak concentration (Cmax)
timeFrame: 1 year
measure: Time to peak concentration (Tmax)
timeFrame: 1 year
measure: Half life (t1/2)
timeFrame: 1 year
measure: Terminal elimination rate constant (Kel)
timeFrame: 1 year
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: 1 year
measure: Progression-Free Survival (PFS)
timeFrame: 6 month
measure: Overall Response Rate (ORR)
timeFrame: 1year
measure: Overall Survival (OS)
timeFrame: 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Baltimore
country: United States
facility: John Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References: