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

• Status: Completed
• Trial end date: 2018-03-20
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Esanex Inc.
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion Criteria:

• 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:

• 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.