Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors

Trial ID or NCT#

NCT02063958

Status

not recruiting iconNOT RECRUITING

Purpose

Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus.

Official Title

A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Everolimus in Subjects With Neuroendocrine Tumors.

Eligibility Criteria

Ages Eligible for Study: Older than 18 Years
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Inclusion Criteria:
  1. - Males or non-pregnant, non-breastfeeding females 18 years-of-age or older. - Archived neuroendocrine tumor sample or biopsy sample (will also be used for genetic testing). - Pathologic evidence of chemo-resistant Small Cell Lung cancer (relapse <90 days after 1st line), chemo-sensitive Small Cell Lung Cancer (relapse >90 days after first line), locally advanced metastatic neuroendocrine tumor of gastro-entero, pancreatic, pulmonary (other than Small Cell Lung) or thymic origin, or advanced renal cell carcinoma for which everolimus is indicated. - Measurable (RECIST) indicator lesion not previously irradiated. - Life expectancy of at least 3 months. - No more than 4 prior lines of systemic anti-cancer therapy. - Karnofsky performance score ≥70. - Adequate baseline laboratory assessments, including - Absolute neutrophil count (ANC) ≥1.5 x 109/L. - WBC >3000/microliter - Platelet count of ≥100 x 109/L. - Total bilirubin level ≤1.5 times institutional upper limit of normal (ULN), alanine aminotransferase or aspartate aminotransferase ≤2 x ULN - Hemoglobin ≥9 mg/dL. - Creatinine <1.5 X upper limit of normal or estimated plasma creatinine clearance of ≥40 mL/min - Signed informed consent form - Recovered from toxicities of previous anticancer therapy - Subjects with reproductive capability must agree to practice adequate contraception methods.
Exclusion Criteria:
  1. - Subjects in whom everolimus is contraindicated. - Subjects with clinically significant interstitial lung disease, or obstructive disease without sufficient reserve - Carcinoid with hormone related symptoms - Neuroendocrine cancer of the thyroid or thymus. - Rare pancreatic neuroendocrine cancers such as, insulinomas, glucagonomas, gastrinomas. - Prior treatment with any Hsp90 inhibitor. - Prior failed treatment with mTOR inhibitors - CNS metastases that are symptomatic and /or requiring escalating doses of steroids. - Major surgery or significant traumatic injury within 4 weeks of starting study treatment. - Conventional chemotherapy or radiation within 4 weeks. - Palliative radiation within 2 weeks. - The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422 - Screening ECG QTc interval ≥470 msec for females, ≥450 msec for males. - At increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-5422; congenital long QT syndrome or a history of torsade de pointes; currently receiving anti-arrhythmics or other medications that may be associated with QT prolongation. - Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management. - Gastrointestinal diseases or conditions that could affect drug absorption, including gastric bypass. - Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis. - History of documented adrenal dysfunction not due to malignancy. - Known seropositive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV). - History of chronic liver disease. - Active hepatitis A or B. - Current alcohol dependence or drug abuse. - Use of an investigational treatment from 30 days prior to the first dose of SNX-5422 and during the study. - Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination. - Other serious concurrent illness or medical condition. - Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.

Investigator(s)

Alice C. Fan
Alice C. Fan
Medical oncologist, Genitourinary specialist
Associate Professor of Medicine (Oncology) and, by courtesy, of Urology
George A. Fisher Jr.
George A. Fisher Jr.
Medical oncologist, Gastrointestinal specialist
Colleen Haas Chair in the School of Medicine

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Contact

Cancer Clinical Trials Office
650-498-7061