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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01635712
Recruitment Status : Completed
First Posted : July 9, 2012
Last Update Posted : April 26, 2017
Information provided by (Responsible Party):
Esanex Inc.

Brief Summary:
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 or disease Intervention/treatment Phase
Cancer Drug: SNX-5422 Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : February 2014
Actual Primary Completion Date : January 2016
Actual Study Completion Date : February 2017

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Number of patients with dose limiting toxicities [ Time Frame: First 28 day cycle ]
    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 :
  1. Number of patients with adverse events as a measure of tolerability [ Time Frame: Day 28 of each cycle ]
    Frequency and severity of AEs, changes in vital signs, ECG, physical examination and clinical chemistry, hematology and urinalysis

  2. Tumor progression [ Time Frame: Completion of every two 28 day cycles ]
    Hematological disease assessment of all known sites of disease using the appropriate hematological malignancy response criteria compared to baseline

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Males or non-pregnant, non-breastfeeding females 18 years-of-age or older with histologically confirmed non-Hodgkins lymphoma, without known or clinically suspected CNS involvement, that is refractory to available therapy or for which there is no available therapy.
  • No more than 4 prior lines of systemic anti-cancer therapy and no prior bone marrow transplant or stem cell transplant within 12 months of dosing, and no prior allogeneic transplant.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01635712

United States, California
UC Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
United States, Georgia
Georgia Regents University Cancer Center
Augusta, Georgia, United States, 30901
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, North Carolina
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Esanex Inc.

Responsible Party: Esanex Inc. Identifier: NCT01635712     History of Changes
Other Study ID Numbers: SNX-5422-CLN1-005
First Posted: July 9, 2012    Key Record Dates
Last Update Posted: April 26, 2017
Last Verified: April 2017

Keywords provided by Esanex Inc.:
Hematological Malignancy

Additional relevant MeSH terms: