Back to resultsSafety and Pharmacology Study of SNX-5422 in Subjects With Refractory Hematological Malignancies
Primary Purpose
Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SNX-5422
Sponsored by
About this trial
This is an interventional treatment trial for Cancer focused on measuring Hematological Malignancy, Hsp90
Eligibility Criteria
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
Sites / Locations
- UC Davis Comprehensive Cancer Center
- Georgia Regents University Cancer Center
- Hackensack University Medical Center
- Wake Forest Baptist Health
- Vanderbilt-Ingram Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SNX-5422
Arm Description
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
Outcomes
Primary Outcome Measures
Number of patients with dose limiting toxicities
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
Frequency and severity of AEs, changes in vital signs, ECG, physical examination and clinical chemistry, hematology and urinalysis
Tumor progression
Hematological disease assessment of all known sites of disease using the appropriate hematological malignancy response criteria compared to baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01635712
Brief Title
Safety and Pharmacology Study of SNX-5422 in Subjects With Refractory Hematological Malignancies
Official Title
A Phase 1, Open-label, Dose-escalation Study of the Safety of SNX-5422 Mesylate in Subjects With Refractory Hematological Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
February 2014 (Actual)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
February 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Esanex Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cancer
Keywords
Hematological Malignancy, Hsp90
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SNX-5422
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
SNX-5422
Intervention Description
Capsule dosed every other day for 21 days out of 28 day cycle. Dose escalation based on safety
Primary Outcome Measure Information:
Title
Number of patients with dose limiting toxicities
Description
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
Time Frame
First 28 day cycle
Secondary Outcome Measure Information:
Title
Number of patients with adverse events as a measure of tolerability
Description
Frequency and severity of AEs, changes in vital signs, ECG, physical examination and clinical chemistry, hematology and urinalysis
Time Frame
Day 28 of each cycle
Title
Tumor progression
Description
Hematological disease assessment of all known sites of disease using the appropriate hematological malignancy response criteria compared to baseline
Time Frame
Completion of every two 28 day cycles
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
UC Davis Comprehensive Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Georgia Regents University Cancer Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30901
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Safety and Pharmacology Study of SNX-5422 in Subjects With Refractory Hematological Malignancies
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