Ignite Creation Date:
2025-12-25 @ 12:05 AM
Ignite Modification Date:
2026-02-25 @ 4:58 PM
Study NCT ID:
NCT02063958
Status:
COMPLETED
Last Update Posted:
2018-07-30
First Post:
2014-02-13
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D018358', 'term': 'Neuroendocrine Tumors'}], 'ancestors': [{'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C561943', 'term': 'SNX-5422'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 19}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-07', 'completionDateStruct': {'date': '2018-03-20', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-07-26', 'studyFirstSubmitDate': '2014-02-13', 'studyFirstSubmitQcDate': '2014-02-13', 'lastUpdatePostDateStruct': {'date': '2018-07-30', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-02-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-03-27', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of patients with dose limiting toxicities', 'timeFrame': 'First 28 day cycle', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Number of patients with adverse events as a measure of tolerability', 'timeFrame': 'Every 4 weeks', 'description': 'Frequency and severity of adverse events'}, {'measure': 'Changes in ECG, vital signs, laboratory or physical examination', 'timeFrame': 'Every 4 weeks', 'description': 'Changes in ECG, vital signs, laboratory or physical examination from baseline'}, {'measure': 'Tumor response', 'timeFrame': 'Every 8 weeks', 'description': "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."}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Neuroendocrine tumor', 'Hsp90'], 'conditions': ['Cancer']}, 'descriptionModule': {'briefSummary': 'Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus.', 'detailedDescription': '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.\n\nThis 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.\n* Archived neuroendocrine tumor sample or biopsy sample (will also be used for genetic testing).\n* 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.\n* Measurable (RECIST) indicator lesion not previously irradiated.\n* Life expectancy of at least 3 months.\n* No more than 4 prior lines of systemic anti-cancer therapy.\n* Karnofsky performance score ≥70.\n* Adequate baseline laboratory assessments, including\n\n * Absolute neutrophil count (ANC) ≥1.5 x 109/L.\n * WBC \\>3000/microliter\n * Platelet count of ≥100 x 109/L.\n * Total bilirubin level ≤1.5 times institutional upper limit of normal (ULN), alanine aminotransferase or aspartate aminotransferase ≤2 x ULN\n * Hemoglobin ≥9 mg/dL.\n * Creatinine \\<1.5 X upper limit of normal or estimated plasma creatinine clearance of ≥40 mL/min\n* Signed informed consent form\n* Recovered from toxicities of previous anticancer therapy\n* Subjects with reproductive capability must agree to practice adequate contraception methods.\n\nExclusion Criteria:\n\n* Subjects in whom everolimus is contraindicated.\n* Subjects with clinically significant interstitial lung disease, or obstructive disease without sufficient reserve\n* Carcinoid with hormone related symptoms\n* Neuroendocrine cancer of the thyroid or thymus.\n* Rare pancreatic neuroendocrine cancers such as, insulinomas, glucagonomas, gastrinomas.\n* Prior treatment with any Hsp90 inhibitor.\n* Prior failed treatment with mTOR inhibitors\n* CNS metastases that are symptomatic and /or requiring escalating doses of steroids.\n* Major surgery or significant traumatic injury within 4 weeks of starting study treatment.\n* Conventional chemotherapy or radiation within 4 weeks.\n* Palliative radiation within 2 weeks.\n* 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\n* Screening ECG QTc interval ≥470 msec for females, ≥450 msec for males.\n* 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.\n* Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.\n* Gastrointestinal diseases or conditions that could affect drug absorption, including gastric bypass.\n* Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.\n* History of documented adrenal dysfunction not due to malignancy.\n* Known seropositive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).\n* History of chronic liver disease.\n* Active hepatitis A or B.\n* Current alcohol dependence or drug abuse.\n* Use of an investigational treatment from 30 days prior to the first dose of SNX-5422 and during the study.\n* Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.\n* Other serious concurrent illness or medical condition.\n* Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process."}, 'identificationModule': {'nctId': 'NCT02063958', 'briefTitle': 'Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors', 'organization': {'class': 'INDUSTRY', 'fullName': 'Esanex Inc.'}, 'officialTitle': 'A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Everolimus in Subjects With Neuroendocrine Tumors.', 'orgStudyIdInfo': {'id': 'SNX5422-CLN-009'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'SNX-5422', 'description': '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.', 'interventionNames': ['Drug: SNX-5422']}], 'interventions': [{'name': 'SNX-5422', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['SNX-5422']}]}, 'contactsLocationsModule': {'locations': [{'zip': '85259-5499', 'city': 'Scottsdale', 'state': 'Arizona', 'country': 'United States', 'facility': 'Mayo Clinic', 'geoPoint': {'lat': 33.50921, 'lon': -111.89903}}, {'zip': '94305', 'city': 'Stanford', 'state': 'California', 'country': 'United States', 'facility': 'Stanford Medicine', 'geoPoint': {'lat': 37.42411, 'lon': -122.16608}}, {'zip': '20007', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Georgetown University Medical Center', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'Center for Cancer Research, National Cancer Institute', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}, {'zip': '07601', 'city': 'Hackensack', 'state': 'New Jersey', 'country': 'United States', 'facility': 'hackensack University Medical Center', 'geoPoint': {'lat': 40.88593, 'lon': -74.04347}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Esanex Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}