Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors
Conditions
Cancer
Conditions: official terms
Apudoma - Carcinoid Tumor - Neuroendocrine Tumors
Conditions: Keywords
Neuroendocrine tumor, Hsp90
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: SNX-5422
Type: Drug
Overall Status
Recruiting
Summary
Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus.
Detailed Description
Heat shock protein 90 (Hsp90) plays a central role in the maturation and maintenance of numerous proteins, for example HER2 and mutated EGFR, that are critical for tumor cell viability and growth; SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone heat shock protein 90 (Hsp90). Hsp90 has been found to be expressed in 95% of subjects with pancreatic neuroendocrine tumors.

This study will determine the MTD of SNX-5422 when given in combination with everolimus in patients with neuroendocrine tumors.The clinical starting dose of 50 mg/m2 qod for SNX-5422 in combination with daily everolimus is 50% of the SNX-5422 qod mono-therapy MTD. The choice to continue once every other day SNX-5422 dosing is based on the safety and efficacy profiles from prior studies, so that drug holidays are interspersed into weekly dosing. The planned subsequent dose levels are 75% and 100% of the SNX-5422 qod mono-therapy MTD.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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.
Locations
Stanford Medicine
Stanford, California, United States
Status: Recruiting
Contact: Pamela L Kunz, MD - 650-725-8738 - pkunz@stanford.edu
Georgetown University Medical Center
Washington, District of Columbia, United States
Status: Not yet recruiting
Contact: Guiseppe Giaccone, MD - 202-687-5791 - gg496@georgetown.edu
Center for Cancer Research, National Cancer Institute
Bethesda, Maryland, United States
Status: Recruiting
Contact: Arlene Berman, RN - 301-435-5609 - arleneb@mail.nih.gov
hackensack University Medical Center
Hackensack, New Jersey, United States
Status: Recruiting
Contact: Martin Gutierrez, MD - 551-996-5900 - mgutierrez@hackensackUMC.org
Start Date
February 2014
Completion Date
January 2016
Sponsors
Esanex Inc.
Source
Esanex Inc.
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page