Trial record 3 of 10 for:    snx5422

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Esanex Inc.
Sponsor:
Information provided by (Responsible Party):
Esanex Inc.
ClinicalTrials.gov Identifier:
NCT01848756
First received: May 3, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Cancer
Drug: SNX-5422
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm, Phase 1/2 Study of SNX-5422 in Subjects With Selected HER2 Positive Cancers.

Resource links provided by NLM:


Further study details as provided by Esanex Inc.:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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 ≥ 6 months) will be listed by subject. Tumor measurements made using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.Progression free survival and overall survival (time frame: every 3 months until 24 months after the last patient has been enrolled) will be listed by subject.


Secondary Outcome Measures:
  • Number of patients with adverse events [ Time Frame: Day 28 of each cycle ] [ Designated as safety issue: Yes ]
    Number and percentage of patients experiencing treatment emergent adverse events described by relationship to treatment and severity.

  • Changes in vital signs, physical examination or clinical laboratory from baseline [ Time Frame: Day 28 of each cycle ] [ Designated as safety issue: Yes ]
    Descriptive summaries of vital signs, physical examination and quantitative clinical laboratory changes will be presented by treatment received and 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.

  • Ophthalmologic changes from baseline [ Time Frame: Day 28 of every 3 cycles ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 35
Study Start Date: April 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01848756

Contacts
Contact: Eric Orlemans, PhD eorlemans@esanexpharma.com

Locations
United States, Arizona
Scottsdale Healthcare Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer, RN MSN    877-273-3713    jschaffer@shc.org   
Principal Investigator: Jasgit Sachdev, MD         
United States, District of Columbia
Georgetown University Medical Center Recruiting
Washington, District of Columbia, United States, 20007
Contact: Giuseppe Giaccone, MD    202-687-5791    gg496@georgetown.edu   
Principal Investigator: Giuseppe Giaccone, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Martin Gutierrez, MD    551-996-5900    mgutierrez@hackensackUMC.org   
Principal Investigator: Martin Gutierrez, MD         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Michelle Maziarz    646-888-4425    maziarzm@mskcc.com   
Contact: Martin H Voss, MD    646-422-4631    vossm@mskcc.com   
Principal Investigator: Martin H Voss, MD         
Sponsors and Collaborators
Esanex Inc.
  More Information

No publications provided

Responsible Party: Esanex Inc.
ClinicalTrials.gov Identifier: NCT01848756     History of Changes
Other Study ID Numbers: SNX-5422-CLN1-008
Study First Received: May 3, 2013
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Esanex Inc.:
SNX-5422
HER2 positive cancer

ClinicalTrials.gov processed this record on August 19, 2014