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

Date de début de l'étude : 1 août 2013

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