Study of SNX-5422 in TP53 Null Cancers
|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
|Condition or disease||Intervention/treatment||Phase|
|Cancer||Drug: SNX-5422||Phase 2|
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)|
|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|
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.
Capsule(s) dosed every other day for 21 days (total 11 doses) out of a 28-day treatment cycle
- 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.
- 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.
- Survival [ Time Frame: Day 28 of each 4 week cycle up to 52 weeks ]Overall survival will be listed by subject at each timepoint
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02612285
|United States, Arizona|
|HonorHealth Research Institute|
|Scottsdale, Arizona, United States, 85258|
|United States, Georgia|
|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|