Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Everolimus in Subjects With Neuroendocrine Tumors.|
- Number of patients with dose limiting toxicities [ Time Frame: First 28 day cycle ] [ Designated as safety issue: Yes ]Number of patients with dose limiting toxicities defined as adverse events or laboratory abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 ≥ Grade 3 that are not clearly related to disease progression or delay by more than 4 weeks in receiving the next scheduled cycle due to persisting toxicities and attributable to the combination of SNX-5422 and everolimus despite optimal medical supportive management.
- Number of patients with adverse events as a measure of tolerability [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]Frequency and severity of adverse events
- Changes in ECG, vital signs, laboratory or physical examination [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]Changes in ECG, vital signs, laboratory or physical examination from baseline
- Tumor response [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]Measurements from tumor imaging within 1 month prior to the screening visit will be used as the baseline assessment. This assessment will be performed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Follow-up imaging of known sites of the disease, preferably by CT scan, will be performed at intervals appropriate to the subject's disease and clinical findings.
|Study Start Date:||February 2014|
|Estimated Study Completion Date:||February 2017|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Open-label administration of SNX-5422 capsules dosed in the morning once every other day (qod) for 21 days (11 doses), followed by a 7 day drug free period. Dose escalation will be based on safety defined as 1 or less dose limiting toxicities during the first 28 day cycle at any dose level. Dose escalation will not exceed a dose of 100 mg/m2 SNX-5422 qod even if the MTD has not been identified. Subjects will receive daily oral everolimus in the PM about the same time every day for 28 days.
Capsule dosed every other day for 21 days out of a 28 day cycle. Dose escalation based on safety not to exceed a dose of 100 mg/m2. Maintenance therapy of SNX-5422 at the MTD will be allowed for all patients not experiencing significant toxicity.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02063958
|United States, Arizona|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, California|
|Stanford, California, United States, 94305|
|United States, District of Columbia|
|Georgetown University Medical Center|
|Washington, District of Columbia, United States, 20007|
|United States, Maryland|
|Center for Cancer Research, National Cancer Institute|
|Bethesda, Maryland, United States, 20892|
|United States, New Jersey|
|hackensack University Medical Center|
|Hackensack, New Jersey, United States, 07601|