CancerPhase 1/2NCT01848756
Safety and Efficacy of SNX-5422 in Human Epidermal Growth Factor Receptor 2 (HER2) Positive Cancers
A Phase 1/2 study testing SNX-5422 in people with Cancer, run by Esanex Inc. at 4 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- SNX-5422
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2013to Jun 2015
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Scottsdale Healthcare
Scottsdale, Arizona, 85258
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
About this study
Official title: A Single Arm, Phase 1/2 Study of SNX-5422 in Subjects With Selected HER2 Positive Cancers.
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.
- Conditions
- Cancer
- Being tested
- SNX-5422
- Keywords
- SNX-5422, HER2 positive cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNX-5422Drug
Capsule(s) dosed every other day for 21 days (total = 11 doses), out of a 28-day treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| SNX-5422 | Experimental | 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. Receives: Drug: SNX-5422 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 24 months from last patient entry
Progression Free Survival
Time on treatment with at worst stable disease.
Measured: Every 3 months until 24 months after the last subject has been enrolled
Overall Survival
Time from start of treatment that patients remain alive.
Measured: Every 3 months until 24 months after the last subject has been enrolled
Secondary outcomes (4)
Number of Patients With Adverse Events
Number of patients experiencing treatment emergent adverse events.
Measured: Day 28 of each cycle
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.
Measured: Day 28 of each cycle
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
Measured: Screening, end of Cycle 1, final visit
Adverse Events by Severity and Relationship to Treatment
Number of patients experiencing adverse events by highest recorded severity and relationship to study tretament
Measured: Every 28 day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2013 (estimated)
- Study startApr 2013
- Primary completionFeb 2015
- Study completionJun 2015
Why it stopped: Business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Esanex Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01848756
- Sponsor's protocol ID
- SNX-5422-CLN1-008
- Status last verified
- Dec 2016
- First submitted
- 3 May 2013
- Last updated
- 9 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Phase 1/2 Study of SNX-5422 in Subjects With Selected HER2 Positive Cancers.
- ClinicalTrials.gov ID
- NCT01848756
- Acronym / sponsor ID
- SNX-5422-CLN1-008
- Conditions
- Cancer
- Keywords
- SNX-5422, HER2 positive cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Esanex Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 7 May 2013 (estimated)
- Results
- Posted 21 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hsp90 is a chemical in the body that is involved in the promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SNX-5422 | Experimental | Drug: SNX-5422Open-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (20 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SNX-5422Capsule(s) dosed every other day for 21 days (total = 11 doses), out of a 28-day treatment cycle. | Drug | SNX-5422 |
Primary outcome
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).
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.
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.
4 secondary outcomes
Number of Patients With Adverse Events
Time frame: Day 28 of each cycle
Changes in Vital Signs, Physical Examination or Clinical Laboratory From Baseline
Time frame: Day 28 of each cycle
Ophthalmologic Changes From Baseline
Time frame: Screening, end of Cycle 1, final visit
Adverse Events by Severity and Relationship to Treatment
Time frame: Every 28 day cycle
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SNX-5422 in people with Cancer, run by Esanex Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Up to 24 months from last patient entry). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2017.