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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Esanex Inc.
Sponsor:
Information provided by (Responsible Party):
Esanex Inc.
ClinicalTrials.gov Identifier:
NCT01892046
First received: June 30, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Cancer
Drug: SNX-5422
Phase 1

Study Type: Interventional
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 Plus Carboplatin and Paclitaxel in Subjects With Selected Solid Tumors.

Resource links provided by NLM:


Further study details as provided by Esanex Inc.:

Primary Outcome Measures:
  • 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 after commencing study treatment that are not clearly related to disease progression


Secondary Outcome Measures:
  • Number of patients with adverse events as a measure of tolerability [ Time Frame: Day 28 of each cycle ] [ Designated as safety issue: Yes ]
    Frequency and severity of adverse events

  • Changes in ECG, vital signs, laboratory or physical examination [ Time Frame: Day 28 of each cycle ] [ Designated as safety issue: Yes ]
    Changes in ECG, vital signs pr physical or laboratory examinations from baseline

  • Tumor response [ Time Frame: Every 12 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 20
Study Start Date: November 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01892046

Contacts
Contact: Eric Orlemans, PhD eorlemans@esanexpharma.com

Locations
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Giuseppe Giaccone, MD    202-687-5791    gg496@georgetown.edu   
Contact: Sharon G Levy, RN    202-687-8921    sgl5@georgetown.edu   
Principal Investigator: Giuseppe Giaccone, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Martin Gutierrez, MD    551-996-5900    mgutierrez@hackensackUMC.org   
Principal Investigator: Martin Gutierrez, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Alexander Drilon, MD    646-497-9163      
Principal Investigator: Alexander Drilon, MD         
Sponsors and Collaborators
Esanex Inc.
  More Information

No publications provided

Responsible Party: Esanex Inc.
ClinicalTrials.gov Identifier: NCT01892046     History of Changes
Other Study ID Numbers: SNX5422-CLN1-006
Study First Received: June 30, 2013
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Esanex Inc.:
Small Cell Lung Cancer
Non Small Cell Lung Cancer
Hsp90

Additional relevant MeSH terms:
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014