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Safety and Efficacy of SNX-5422 in Human Epidermal Growth Factor Receptor 2 (HER2) Positive Cancers

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: NCT01848756
Recruitment Status : Terminated (Business reasons)
First Posted : May 7, 2013
Results First Posted : November 21, 2016
Last Update Posted : February 9, 2017
Information provided by (Responsible Party):
Esanex Inc.

Brief Summary:
Hsp90 is a chemical in the body that is involved in the promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90

Condition or disease Intervention/treatment Phase
Cancer Drug: SNX-5422 Phase 1 Phase 2

Detailed Description:
Heat shock protein 90 (Hsp90) chaperone proteins stabilize well over 200 different known client proteins helping them to fold correctly as they take up their rightful positions in the cell. Hsp90 has a special fondness for oncoproteins whose structures shift according to functional state. Among Hsp90's clients, a surprising number are well recognized targets in oncology, including human epidermal growth factor receptor 2 (HER2). 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). Treatment of HER2-positive cell lines such as BT-474 with the Hsp90 inhibitor SNX-2112 results in cellular degradation, decreased levels of phospho-AKT/cyclin D1, and increased apoptosis. Furthermore, treatment with SNX-5542 caused tumor regression, including remission in a HER2-overexpressing breast cancer xenograft model. SNX-5422 has demonstrated significant antitumor activity in mouse xenograft models of various human malignancies, including breast (BT474, MX-1), lung (H1975, H1650, EBC-1), colon (HT29), prostate (PC3), and melanoma (A375) with multiple oral dosing regimens.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Phase 1/2 Study of SNX-5422 in Subjects With Selected HER2 Positive Cancers.
Study Start Date : April 2013
Actual Primary Completion Date : February 2015
Actual Study Completion Date : June 2015

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), out of a 28-day treatment cycle. Subjects will continue treatment on a 28-day cycle at the discretion of the principal investigator based on safety.
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. Objective Response Rate [ Time Frame: Up to 24 months from last patient entry ]
    The effect of SNX-5422 on tumor progression. Objective tumor responses (complete remissions plus partial remissions) and clinical benefit rate (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).

  2. Progression Free Survival [ Time Frame: Every 3 months until 24 months after the last subject has been enrolled ]
    Time on treatment with at worst stable disease.

  3. Overall Survival [ Time Frame: Every 3 months until 24 months after the last subject has been enrolled ]
    Time from start of treatment that patients remain alive.

Secondary Outcome Measures :
  1. Number of Patients With Adverse Events [ Time Frame: Day 28 of each cycle ]
    Number of patients experiencing treatment emergent adverse events.

  2. Changes in Vital Signs, Physical Examination or Clinical Laboratory From Baseline [ Time Frame: Day 28 of each cycle ]
    Descriptive summaries of vital signs, physical examination and clinical laboratory changes will be presented by treatment received.

  3. Ophthalmologic Changes From Baseline [ Time Frame: Screening, end of Cycle 1, final visit ]
    Ophthalmologic assessments will be presented by cohort, study visit and dose. Number of subjects experiencing clinically relevant changes from baseline in any of these examinations will be presented using descriptive summary

  4. Adverse Events by Severity and Relationship to Treatment [ Time Frame: Every 28 day cycle ]
    Number of patients experiencing adverse events by highest recorded severity and relationship to study tretament

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  • Males or non-pregnant, non-breastfeeding females .
  • Confirmed diagnosis of locally advanced or metastatic breast, esophagogastric, urothelial, or non-small cell lung cancer.
  • Histological or cytological confirmed carcinoma with HER2 amplification (IHC 3+ or FISH+ (>2 HER2:CEP17)).
  • Subjects with advanced or metastatic breast cancer must have received no more than 5 prior lines of anticancer therapy, including trastuzumab (but excluding hormonal treatments).
  • Subjects with advanced or metastatic HER2 positive esophagogastric cancer must have received no more than 5 prior lines of anticancer therapy, including trastuzumab.
  • Subjects with advanced or metastatic, urothelial carcinoma or non-small cell lung cancer must have received at least one, but no more than 5 prior lines of anticancer therapy.
  • Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Life expectancy of at least 3 months.
  • Karnofsky performance score ≥70.
  • Adequate baseline laboratory assessments
  • Recovered from toxicities of previous anticancer therapy, with the exception of CTCAE grade 1 sensory neuropathy.

Exclusion Criteria:

  • Subjects with symptomatic central nervous system (CNS) metastases who are neurologically unstable
  • Prior treatment with any Hsp90 inhibitor.
  • Surgery, radiotherapy, or lesion ablative procedure to the only area of measurable disease.
  • Major surgery within 4 weeks prior to first dose of SNX-5422.
  • Treatment with chronic immunosuppressants (e.g., cyclosporine following transplantation).
  • 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.
  • Screening ECG QTc interval ≥470 msec for females, ≥450 msec for males.
  • At increased risk for developing prolonged QT interval
  • Patients with chronic diarrhea or with grade 2 or greater diarrhea 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.
  • Known 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.
  • Treatment with other anticancer drugs within 28 days or 5 half-lives of anticancer therapy (whichever is shorter), and treatment with any other investigational agent is prohibited from 30 days prior to the first dose of SNX-5422 and throughout the study
  • Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination.
  • Other serious concurrent illness or medical condition.
  • Psychological, social, familial, or geographical reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.

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): NCT01848756

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United States, Arizona
Scottsdale Healthcare
Scottsdale, Arizona, United States, 85258
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Esanex Inc.
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Responsible Party: Esanex Inc. Identifier: NCT01848756    
Other Study ID Numbers: SNX-5422-CLN1-008
First Posted: May 7, 2013    Key Record Dates
Results First Posted: November 21, 2016
Last Update Posted: February 9, 2017
Last Verified: December 2016
Keywords provided by Esanex Inc.:
HER2 positive cancer