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Trial record 3 of 13 for:    snx5422

Study of SNX-5422 in TP53 Null Cancers

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ClinicalTrials.gov Identifier: NCT02612285
Recruitment Status : Terminated (Recruitment very slow - study could not be enrolled)
First Posted : November 23, 2015
Last Update Posted : November 4, 2016
Sponsor:
Information provided by (Responsible Party):
Esanex Inc.

Brief Summary:
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). Initial in vitro evidence supports that SNX-5422 may be active against TP53 null tumors irrespective of tumor type .

Condition or disease Intervention/treatment Phase
Cancer Drug: SNX-5422 Phase 2

Detailed Description:

The tumor suppressor gene TP53 codes for a central regulator of the DNA-damage-response pathway, and its activation leads to cell-cycle arrest and DNA repair, apoptosis, or senescence through both transcription-dependent and transcriptional-independent activities. Somatic TP53 gene alterations are frequent in most human cancers.

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). Inhibitors of the chaperone protein Hsp90 are of current interest because of the central role that Hsp90 plays in the maturation and maintenance of numerous proteins that are critical for tumor cell viability and growth.

SNX-2112 retains activity in cell lines with loss of the TP53 gene from one of the alleles. SNX-2112 displays good activity in cell lines with TP53 null/TP53 wild type (e.g., MEC-1 [chronic lymphocytic leukemia]) and TP53 null/TP53 mutation (e.g., EBC-1, NCI-H520 [all NSCLC - squamous cell carcinoma]). Even in the most extreme case in which TP53 is lost from both alleles, i.e., the cancer cell is totally devoid of the TP53 gene (e.g., H1299, KATO III, HL-60, SK-MES-1), SNX-2112 retains activity

It appears that SNX-2112 could be active against both hematological and solid tumors with a TP53 null status.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm Study of SNX-5422 in Subjects With TP53 Null Cancers
Study Start Date : March 2016
Primary Completion Date : October 2016
Study Completion Date : October 2016

Arm Intervention/treatment
Experimental: SNX-5422
Open-label administration of SNX‑5422 capsules to total 100 mg/m2 every other day for 21 days (total = 11 doses), followed by a 7‑day drug‑free period. Each treatment cycle will be 28 days. Subjects will repeat this 28-day schedule until the cancer progresses or the subject is unable to tolerate SNX-5422.
Drug: SNX-5422
Capsule(s) dosed every other day for 21 days (total 11 doses) out of a 28-day treatment cycle



Primary Outcome Measures :
  1. Clinical Response Rate [ Time Frame: 6 months ]
    Effect of SNX-5422 on tumor progression. Complete remissions plus partial remissions plus stable disease at ≥6 months) will be listed by subject. Tumor measurements made using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or appropriate hematological malignancy criteria.


Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: 6 months ]
    Effect of SNX-5422 on tumor progression. Complete remissions plus partial remissions at ≥6 months) will be listed by subject. Tumor measurements made using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or appropriate hematological malignancy criteria.

  2. Survival [ Time Frame: Day 28 of each 4 week cycle up to 52 weeks ]
    Overall survival will be listed by subject at each timepoint

  3. Changes in vital signs, physical examination or clinical laboratory parameters from baseline [ Time Frame: Day 28 of each 4 week cycle from randomization up to 52 weeks ]
    Descriptive summaries of vital signs, physical examination and quantitative clinical laboratory values and changes from baseline will be presented by study visit. Laboratory toxicities will be graded by severity using common terminology criteria for adverse events (CTCAE) Version 4.03. Frequency and percentage of subjects experiencing clinically relevant toxicities will be summarized by treatment received. Summaries may be repeated by treatment cycle.



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

Inclusion Criteria:

  • Confirmed solid or hematological TP53 null type cancer.
  • No more than 4 prior lines of systemic anti-cancer therapy.
  • Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.
  • Karnofsky performance score 60
  • Life expectancy of at least 3 months.
  • Adequate baseline laboratory assessments
  • Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia.

Exclusion Criteria:

  • Treatment with an investigational agent within 30 days prior to the first dose of SNX‑5422 or planning to receive an investigational agent during the study.
  • Treatment with other anticancer drugs within 28 days or 5 half-lives of anticancer therapy (whichever is shorter) is prohibited from 30 days prior to the first dose of SNX-5422 and throughout the study.
  • Radiation treatment within 2 weeks.
  • 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 (Appendix B).
  • Appropriately corrected screening ECG QTc interval 470 msec for females, 450 msec for males.
  • Currently receiving medications known to cause QT prolongation AND corrected QTc of 450 msec for females, 430 msec for males.
  • Patients with chronic diarrhea of grade 2 or greater 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.
  • 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.
  • Clinically significant glaucoma, retinitis pigmentosa, or macular degeneration.
  • Other serious concurrent illness or medical condition.

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 ClinicalTrials.gov identifier (NCT number): NCT02612285


Locations
United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
United States, Georgia
Augusta University
Augusta, Georgia, United States, 30912
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Ohio
Gabrail Cancer Center Research
Canton, Ohio, United States, 44718
Wexner Medical Center, Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Esanex Inc.

Responsible Party: Esanex Inc.
ClinicalTrials.gov Identifier: NCT02612285     History of Changes
Other Study ID Numbers: SNX-5422-CLN2-010
First Posted: November 23, 2015    Key Record Dates
Last Update Posted: November 4, 2016
Last Verified: November 2016