CClinicalTrials.gg
Sign In
TerminatedNCT01848756Updated Feb 9, 2017Results posted

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

A Phase 1/2 interventional study of SNX-5422 in Cancer, sponsored by Esanex Inc.. Terminated at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-02-09.

Sponsored by Esanex Inc. · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Business reasons
Phase
Phase 1/2
Study type
Interventional
Enrollment
15
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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

Read the 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.

02

Conditions studied

  • Cancer

Keywords

  • SNX-5422
  • HER2 positive cancer
03

In context

Lead sponsor

Esanex Inc. is the lead sponsor of 12 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
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

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.
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (actual)

Study arms

  • 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

Interventions

  • DrugSNX-5422

    Capsule(s) dosed every other day for 21 days (total = 11 doses), out of a 28-day treatment cycle.

06

What researchers measure

Primary outcomes

  1. Objective Response Rate

    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).

    Time frame: Up to 24 months from last patient entry

  2. Progression Free Survival

    Time on treatment with at worst stable disease.

    Time frame: Every 3 months until 24 months after the last subject has been enrolled

  3. Overall Survival

    Time from start of treatment that patients remain alive.

    Time frame: Every 3 months until 24 months after the last subject has been enrolled

Secondary outcomes

  1. Number of Patients With Adverse Events

    Number of patients experiencing treatment emergent adverse events.

    Time frame: Day 28 of each cycle

  2. Changes in Vital Signs, Physical Examination or Clinical Laboratory From Baseline

    Descriptive summaries of vital signs, physical examination and clinical laboratory changes will be presented by treatment received.

    Time frame: Day 28 of each cycle

  3. Ophthalmologic Changes From Baseline

    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

    Time frame: Screening, end of Cycle 1, final visit

  4. Adverse Events by Severity and Relationship to Treatment

    Number of patients experiencing adverse events by highest recorded severity and relationship to study tretament

    Time frame: Every 28 day cycle

07

Results

Posted Nov 21, 2016

Participant flow

Participant flow — Overall Study
MilestoneSNX-5422
Started15
Completed12
Not completed3
Withdrew: Adverse event1
Withdrew: Withdrawal by subject1
Withdrew: Enrolled in error1

Outcome measures

PrimaryObjective Response Rate

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).

Time frame:
Up to 24 months from last patient entry

No measurements were reported for this outcome.

PrimaryProgression Free Survival

Time on treatment with at worst stable disease.

Time frame:
Every 3 months until 24 months after the last subject has been enrolled

No measurements were reported for this outcome.

PrimaryOverall Survival

Time from start of treatment that patients remain alive.

Time frame:
Every 3 months until 24 months after the last subject has been enrolled

No measurements were reported for this outcome.

SecondaryNumber of Patients With Adverse Events

Number of patients experiencing treatment emergent adverse events.

Time frame:
Day 28 of each cycle
Reported as:
Number · participants
Number of Patients With Adverse Events
participantsSNX-5422
Number of Patients With Adverse Events15
SecondaryChanges in Vital Signs, Physical Examination or Clinical Laboratory From Baseline

Descriptive summaries of vital signs, physical examination and clinical laboratory changes will be presented by treatment received.

Time frame:
Day 28 of each cycle
Reported as:
Number · participants
Changes in Vital Signs, Physical Examination or Clinical Laboratory From Baseline
participantsSNX-5422
All laboratory abnormalities8
ALT/AST increases6
Alkaline phosphatase increase3
Vital signs0
Systolic/diastolic blood pressure0
Respiratory rate0
Temperature0
ECG0
SecondaryOphthalmologic Changes From Baseline

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

Time frame:
Screening, end of Cycle 1, final visit
Reported as:
Number · participants
Ophthalmologic Changes From Baseline
participantsSNX-5422
Ophthalmologic Changes From Baseline1
SecondaryAdverse Events by Severity and Relationship to Treatment

Number of patients experiencing adverse events by highest recorded severity and relationship to study tretament

Time frame:
Every 28 day cycle
Reported as:
Number · participants
Adverse Events by Severity and Relationship to Treatment
participantsSNX-5422
Subjects with adverse events15
Subjects with Grade 3 or 4 adverse events8
Subjects with Grade 5 adverse events2
Subjects with treatment related adverse events15
Subjects with Grade 3 or 4 AEs related to treatmen7
Subjects with Grade 5 AEs related to treatment0

Adverse events

Collected over From patient screening to removal from study, average time on study 49+/-16 days. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
SNX-5422—8/15 (53.3%)15/15 (100%)
Most frequent serious events
Showing 10 of 15
Most frequent serious events
EventSNX-5422
Renal Failure AcuteRenal and urinary disorders2/15
Abdominal Pain UpperGastrointestinal disorders1/15
Atrial FibrillationCardiac disorders1/15
DiarrhoeaGastrointestinal disorders1/15
HaematemesisGastrointestinal disorders1/15
NauseaGastrointestinal disorders1/15
VomitingGastrointestinal disorders1/15
Cardiac TamponadeCardiac disorders1/15
Pericardial EffusionCardiac disorders1/15
PneumoniaInfections and infestations1/15
Most frequent other events
Showing 10 of 34
Most frequent other events
EventSNX-5422
DiarrhoeaGastrointestinal disorders13/15
NauseaGastrointestinal disorders8/15
VomitingGastrointestinal disorders8/15
FatigueGeneral disorders6/15
Aspartate Aminotransferase increasedInvestigations5/15
AnaemiaBlood and lymphatic system disorders4/15
Abdominal PainGastrointestinal disorders3/15
Decreased AppetiteMetabolism and nutrition disorders3/15
Alanine Aminotransferase IncreasedInvestigations3/15
ConstipationGastrointestinal disorders2/15

Baseline characteristics

Age, Continuous
Age, Continuous(years)SNX-5422
Mean58 ± 12.9
Gender
Gender(Participants)SNX-5422
Female9
Male6
Race (NIH/OMB)
Race (NIH/OMB)(Participants)SNX-5422
American Indian or Alaska Native0
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American0
White13
More than one race1
Unknown or Not Reported0
08

Study locations

4 sites
  • Scottsdale Healthcare
    Scottsdale, Arizona 85258, United States
  • Georgetown University Medical Center
    Washington, District of Columbia 20007, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • Memorial Sloan-Kettering Cancer Center
    New York, New York 10065, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 9, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01848756
Lead sponsor
Esanex Inc.
Responsible party
Sponsor
First posted
May 7, 2013
Start date
Apr 2013
Primary completion
Feb 2015
Completion
Jun 2015
Results posted
Nov 21, 2016
Last update
Feb 9, 2017

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Dec 2016. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies from this sponsor

Esanex Inc.

Start the discussion