Safety and Pharmacology Study of SNX-5422 in Subjects With Refractory Hematological Malignancies

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:
NCT01635712
First received: July 4, 2012
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

Hsp90 is a chemical in the body that is involved int he 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 the Safety of SNX-5422 Mesylate in Subjects With Refractory Hematological Malignancies

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 AEs or laboratory abnormalities of Common Terminology Criteria for Adverse Events [CTCAE] version 4.03 ≥ Grade 3 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 AEs, changes in vital signs, ECG, physical examination and clinical chemistry, hematology and urinalysis

  • Tumor progression [ Time Frame: Completion of every two 28 day cycles ] [ Designated as safety issue: No ]
    Hematological disease assessment of all known sites of disease using the appropriate hematological malignancy response criteria compared to baseline


Estimated Enrollment: 16
Study Start Date: February 2014
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: April 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 on 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
Drug: SNX-5422
Capsule dosed every other day for 21 days out of 28 day cycle. Dose escalation based on safety

Detailed Description:

SNX-5422 is a prodrug for SNX-2112. Correlation has been observed between Hsp90 client protein level changes and functional effects in cells in in vitro studies of SNX-2112, supporting inhibition of Hsp90 as the mechanism of action for this compound. SNX-5422 has demonstrated significant antitumor activity in mouse xenograft models of human tumors, including breast (BT474, MX-1), colon (HT29), prostate (PC3), and melanoma (A375) with multiple oral dosing regimens. Pharmacokinetic (PK) studies in mice, rats, and dogs have shown high bioavailability of SNX-2112 following oral administration of SNX 5422. In mouse xenograft studies, SNX-2112 was selectively retained in tumor tissue compared with other tissues. This study will employ critical risk management features including the use of the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03, which provides a scale for consistently grading the severity of AEs, toxicity criteria analyses for dose escalation, frequent laboratory and clinical observations, correlation of AEs with plasma concentrations of SNX-5422 and SNX-2112, monitoring of the QTc interval at appropriate time points, and a conservative dose-escalation scheme.

  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 with confirmed hematological malignancy, without known or clinically suspected CNS involvement, that is refractory to available therapy or for which there is no available therapy.
  • Karnofsky performance score ≥60
  • Life expectancy of at least 3 months.
  • Adequate baseline laboratory assessments

Exclusion Criteria:

  • Currently receiving anticancer therapy or have received anticancer therapy within the past 28 days or 5 half-lives of the anticancer therapy
  • 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
  • At increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-• Chronic diarrhea.
  • 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.
  • Seropositive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV).
  • History of chronic liver disease
  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: NCT01635712

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

Locations
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, Tennessee
Vanderbilt-Ingram Cancer Center Recruiting
Nashville, Tennessee, United States, 37212
Contact: CTIP Department    800-811-8480      
Principal Investigator: Nishitha M Reddy, MD         
Sponsors and Collaborators
Esanex Inc.
  More Information

No publications provided

Responsible Party: Esanex Inc.
ClinicalTrials.gov Identifier: NCT01635712     History of Changes
Other Study ID Numbers: SNX-5422-CLN1-005
Study First Received: July 4, 2012
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Esanex Inc.:
Hematological Malignancy
Hsp90

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 02, 2014