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Safety and Pharmacology of SNX-5422 Plus Carboplatin and Paclitaxel in Subjects With Solid Tumors

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ClinicalTrials.gov Identifier: NCT01892046
Recruitment Status : Completed
First Posted : July 3, 2013
Last Update Posted : July 26, 2017
Sponsor:
Information provided by (Responsible Party):
Esanex Inc.

Tracking Information
First Submitted Date  ICMJE June 30, 2013
First Posted Date  ICMJE July 3, 2013
Last Update Posted Date July 26, 2017
Study Start Date  ICMJE November 2013
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2013)
Number of patients with dose limiting toxicities [ Time Frame: First 28 day cycle ]
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 after commencing study treatment that are not clearly related to disease progression
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01892046 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2013)
  • Number of patients with adverse events as a measure of tolerability [ Time Frame: Day 28 of each cycle ]
    Frequency and severity of adverse events
  • Changes in ECG, vital signs, laboratory or physical examination [ Time Frame: Day 28 of each cycle ]
    Changes in ECG, vital signs pr physical or laboratory examinations from baseline
  • Tumor response [ Time Frame: Every 12 weeks ]
    Tumor response using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (version 1.0) assessed by CT scan (or MRI) when combined with carboplatin and paclitaxel and for SNX-5422 when given alone during the maintenance part.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Pharmacology of SNX-5422 Plus Carboplatin and Paclitaxel in Subjects With Solid Tumors
Official Title  ICMJE A Phase 1, Open-label, Dose-escalation Study of SNX 5422 Plus Carboplatin and Paclitaxel in Subjects With Selected Solid Tumors.
Brief Summary Heat shock protein 90 (Hsp90) is a chemical in the body that is involve in the promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90.
Detailed Description Heat shock protein 90 (Hsp90) chaperone proteins stabilize well over 200 different known client proteins helping them to fold correctly as they take up their rightful positions in the cell. Inhibitors of the chaperone protein Hsp90 are of current interest because of the central role of Hsp90 in the maturation and maintenance of numerous proteins 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). The study will determine the maximum tolerated dose (MTD) of SNX-5422 when combined with carboplatin plus paclitaxel in selected solid tumors and assess the safety and efficacy of SNX-5422 alone dosed at the MTD as maintenance therapy in selected solid tumors treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cancer
Intervention  ICMJE Drug: SNX-5422
Capsule dosed every other day for 21 days out of a 28 day cycle. Dose escalation based on safety. Maintenance doses at the maximum tolerated dose.
Study Arms  ICMJE Experimental: SNX-5422
Open label administration of SNX-5422 capsules every other day (QOD) for 21 days of a 28 day cycle. Dose escalation will be based on safety outcomes defined as 1 or less dose limiting toxicities during the first 28 day cycle at any dose level. During the dose escalation phase, subjects will receive carboplatin and paclitaxel once every 21 days for a total of 4 courses. During the maintenance phase, SNX-5422 at the MTD will be dosed every other day (QOD) for 21 days of a 28 day cycle.
Intervention: Drug: SNX-5422
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 23, 2016)
18
Original Estimated Enrollment  ICMJE
 (submitted: June 30, 2013)
20
Actual Study Completion Date  ICMJE July 2017
Actual Primary Completion Date February 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.
  • Pathologic evidence of Small Cell Lung Cancer, or Non-Small Cell Lung Cancer.
  • No more than one prior line of antitumor therapy for metastatic disease, excluding prior treatment with tyrosine kinase inhibitors. An interval of at least 1 week is required for washout of the tyrosine kinase inhibitor.
  • Measurable disease using RECIST criteria (version 1.1).
  • Life expectancy of at least 3 months.
  • 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 (ALT) or aspartate aminotransferase (AST) ≤2.0 x ULN except in subjects with known hepatic metastasis, where AST or ALT can be ≤5.0 x ULN.
    • Hemoglobin ≥9 mg/dL.
    • Estimated creatinine clearance of ≥40 mL/min
  • Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia.
  • Signed informed consent form (ICF)
  • Subjects with reproductive capability must agree to practice adequate contraception methods.
  • Adequate venous access

Exclusion Criteria:

  • CNS metastases that are symptomatic and /or requiring steroids.
  • Prior treatment with any Hsp90 inhibitor.
  • Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
  • 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 maximal 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.
  • Treatment with other anticancer drugs within 28 days or 5 half-lives of anticancer therapy (whichever is shorter), and treatment with any other investigational agent is prohibited from 30 days prior to the first dose of SNX-5422 and throughout the study.
  • Radiation treatment within 2 weeks.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01892046
Other Study ID Numbers  ICMJE SNX5422-CLN1-006
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Esanex Inc.
Study Sponsor  ICMJE Esanex Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Esanex Inc.
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP