Clinical Trials /

Study of SNX-5422 in TP53 Null Cancers

NCT02612285

Description:

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 .

Related Conditions:
  • Cancer
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">SNX-5422</span> in <span class="go-doc-concept go-doc-biomarker">TP53</span> Null Cancers

Title

  • Brief Title: Study of SNX-5422 in TP53 Null Cancers
  • Official Title: A Single Arm Study of SNX-5422 in Subjects With TP53 Null Cancers
  • Clinical Trial IDs

    NCT ID: NCT02612285

    ORG ID: SNX-5422-CLN2-010

    Trial Conditions

    Cancer

    Trial Interventions

    Drug Synonyms Arms
    SNX-5422 SNX-5422

    Trial Purpose

    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 .

    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.

    Trial Arms

    Name Type Description Interventions
    SNX-5422 Experimental Open-label administration of SNX5422 capsules to total 100 mg/m2 every other day for 21 days (total = 11 doses), followed by a 7day drugfree 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. SNX-5422

    Eligibility 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
    SNX5422 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Clinical Response Rate

    Secondary Outcome Measures

    Objective Response Rate

    Survival

    Changes in vital signs, physical examination or clinical laboratory parameters from baseline

    Trial Keywords