CancerPhase 2NCT02612285
Study of SNX-5422 in TP53 Null Cancers
A Phase 2 study testing SNX-5422 in people with Cancer, run by Esanex Inc. at 5 sites in United States.
Trial summary
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 . 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
- 1 participants
- Where
- 5 sitesUnited States
- Study dates
- Mar 2016to Oct 2016
- Phase
- Phase 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
- 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.
Who cannot join
- Treatment with an investigational agent within 30 days prior to the first dose of SNX-5422 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.
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- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Augusta University
Augusta, Georgia, 30912
Gabrail Cancer Center Research
Canton, Ohio, 44718
Wexner Medical Center, Ohio State University
Columbus, Ohio, 43210
Karmanos Cancer Institute
Detroit, Michigan, 48201
HonorHealth Research Institute
Scottsdale, Arizona, 85258
About this study
Official title: A Single Arm Study of SNX-5422 in Subjects With TP53 Null 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). Initial in vitro evidence supports that SNX-5422 may be active against TP53 null tumors irrespective of tumor type .
Read the 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.
- Conditions
- Cancer
- Being tested
- SNX-5422
- 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), followed by a 7-day drug-free 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. Receives: Drug: SNX-5422 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response Rate
Effect of SNX-5422 on tumor progression. 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 1.1) or appropriate hematological malignancy criteria.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2015 (estimated)
- Study startMar 2016
- Primary completionOct 2016
- Study completionOct 2016
Why it stopped: Recruitment very slow - study could not be enrolled
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 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
- NCT02612285
- Sponsor's protocol ID
- SNX-5422-CLN2-010
- Status last verified
- Oct 2018
- First submitted
- 19 Nov 2015
- Last updated
- 14 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Study of SNX-5422 in Subjects With TP53 Null Cancers
- ClinicalTrials.gov ID
- NCT02612285
- Acronym / sponsor ID
- SNX-5422-CLN2-010
- Conditions
- Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment very slow - study could not be enrolled
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Esanex Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2016
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 23 Nov 2015 (estimated)
- Results
- Posted 14 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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), followed by a 7-day drug-free 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- Treatment with an investigational agent within 30 days prior to the first dose of SNX-5422 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.
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
Clinical Response Rate
Time frame: 6 months
Effect of SNX-5422 on tumor progression. 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 1.1) or appropriate hematological malignancy criteria.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2018.
- 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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SNX-5422 in people with Cancer, run by Esanex Inc. at 5 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 7 inclusion and 16 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 14 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 phase mean?
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 14 Nov 2018). 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?
Clinical Response Rate (time frame: 6 months). 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 14 Nov 2018.