CancerPhase 1NCT01851096
Safety and Pharmacology Study of SNX-5422 in Subjects With Resistant Lung Adenocarcinoma
A Phase 1 study testing SNX-5422 in people with Cancer, run by Esanex Inc. at 2 sites in United States.
Trial summary
Heat shock protein 90 (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
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2013to Aug 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years-of-age or older.
- Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time.
- Must have undergone a biopsy after the development of acquired resistance.
- Pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically
- Radiographic progression by RECIST during treatment with erlotinib/gefitinib.
- Measurable (RECIST) indicator lesion not previously irradiated.
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- No more than 4 prior lines of cytotoxic chemotherapy, including erlotinib/gefitinib
- Karnofsky performance score ≥70.
- Adequate baseline laboratory assessments, including
- Absolute neutrophil count (ANC) ≥1.5 x 109/L.
- WBC >3000/microliter
- Platelet count of ≥100 x 109/L.
- Total bilirubin level ≤1.5 times institutional upper limit of normal (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤1.5 x ULN.
- Hemoglobin ≥9 mg/dL.
- Creatinine <1.5 X upper limit of normal or estimated plasma creatinine clearance of ≥40 mL/min (using the Cockroft-Gault equation)
- Signed informed consent form (ICF).
- Subjects with reproductive capability must agree to practice adequate contraception methods.
- Adequate venous access.
Who cannot join
- CNS metastases which are symptomatic and /or requiring escalating doses of steroids.
- Prior treatment with any Hsp90 inhibitor.
- Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed).
- Palliative radiation 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
- Screening ECG QTc interval ≥470 msec for females, ≥450 msec for males.
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- At increased risk for developing prolonged QT interval, including hypokalemia or hypomagnesemia, unless corrected to within normal limits prior to first dose of SNX-5422; congenital long QT syndrome or a history of torsade de pointes; currently receiving anti-arrhythmics or other medications that may be associated with QT prolongation.
- 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.
- Use of an investigational treatment from 30 days prior to the first dose of SNX-5422 and during 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
2 sites in 1 country.
United States2 sites
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
About this study
Official title: A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Erlotinib in Subjects With Lung Adenocarcinoma With "Acquired Resistance" to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.
Heat shock protein 90 (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 many client proteins including mutant EGFR, and are also hypothesized to help maintain the malignant phenotype of mutant EGFR in lung adenocarcinoma. Treatment of EGFR mutant cell lines with the Hsp90 inhibitor geldanamycin results in cellular degradation, decreased levels of pAKT/cyclin D1, and increased apoptosis. Furthermore, Hsp90 inhibitors hamper growth of tumors in nude mice with gefitinib-resistant H1975-xenografts in vivo.
Clinical data showed that mono-therapy with some Hsp90 inhibitors provides stable disease and some patients have partial remissions as best responses in heavily pre-treated non small cell lung cancer patients.
SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone 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, for example HER2 and mutated EGFR, that are critical for tumor cell viability and growth.
- Conditions
- Cancer
- Being tested
- SNX-5422
- Keywords
- Hsp90, SNX-5422, Erlotinib, Lung adenocarcinoma
- Medical subject headings
- Neoplasms, Adenocarcinoma of Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNX-5422Drug
Capsules dosed every other day in the morning starting at a dose of 50 mg/m2. Dose escalation based on safety. Subjects will also receive 150 mg erlotinib daily (in the afternoon).
| Study group | Role | What they receive |
|---|---|---|
| SNX-5422 | Experimental | Open label administration of SNX-5422 tablets every other day for 21 days on a 28 day cycle. Dose escalation of SNX-5422 based on safety outcomes Receives: Drug: SNX-5422 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with dose limiting toxicities
Number of patients with dose limiting toxicities defined as adverse events (AE) or laboratory abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) version 4.03 ≥ Grade 3 that are not clearly related to disease progression
Measured: Day 28 of first dose cycle
Secondary outcomes (3)
Tumor response
Tumor progression relative to baseline; assessment of tumor response will be performed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Measured: Weeks 4, 12, 20 and 28
Changes in vital signs, physical examination or clinical laboratory from baseline
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.
Measured: Weeks 4, 8, 12, 16, 20, 24 and 28
Number of patients with ophthalmological changes from baseline
Ophthalmologic assessments (visual acuity, visual field, ophthalmoscopy, dark adaptation, optical coherence tomography) 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: Weeks 4, 16 and 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study startMar 2013
- Primary completionOct 2015
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 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
- NCT01851096
- Sponsor's protocol ID
- SNX-5422-CLN1-007
- Status last verified
- Aug 2016
- First submitted
- 4 May 2013
- Last updated
- 16 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: Phase 1 pharmacology study
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Erlotinib in Subjects With Lung Adenocarcinoma With "Acquired Resistance" to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.
- ClinicalTrials.gov ID
- NCT01851096
- Acronym / sponsor ID
- SNX-5422-CLN1-007
- Conditions
- Cancer
- Keywords
- Hsp90, SNX-5422, Erlotinib, Lung adenocarcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Esanex Inc.Industry (pharma, biotech, devices)
- Study start
- Mar 2013
- Primary completion
- Oct 2015 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 10 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heat shock protein 90 (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 many client proteins including mutant EGFR, and are also hypothesized to help maintain the malignant phenotype of mutant EGFR in lung adenocarcinoma. Treatment of EGFR mutant cell lines with the Hsp90 inhibitor geldanamycin results in cellular degradation, decreased levels of pAKT/cyclin D1, and increased apoptosis. Furthermore, Hsp90 inhibitors hamper growth of tumors in nude mice with gefitinib-resistant H1975-xenografts in vivo.
Clinical data showed that mono-therapy with some Hsp90 inhibitors provides stable disease and some patients have partial remissions as best responses in heavily pre-treated non small cell lung cancer patients.
SNX-5422 is a pro-drug of SNX-2112, a potent, highly selective, small-molecule inhibitor of the molecular chaperone 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, for example HER2 and mutated EGFR, that are critical for tumor cell viability and growth.
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 tablets every other day for 21 days on a 28 day cycle. Dose escalation of SNX-5422 based on safety outcomes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.
- Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time.
- Must have undergone a biopsy after the development of acquired resistance.
- Pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically
- Radiographic progression by RECIST during treatment with erlotinib/gefitinib.
Key exclusion criteria (19 listed)
- CNS metastases which are symptomatic and /or requiring escalating doses of steroids.
- Prior treatment with any Hsp90 inhibitor.
- Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed).
- Palliative radiation 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
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-5422Capsules dosed every other day in the morning starting at a dose of 50 mg/m2. Dose escalation based on safety. Subjects will also receive 150 mg erlotinib daily (in the afternoon). | Drug | SNX-5422 |
Primary outcome
Number of patients with dose limiting toxicities
Time frame: Day 28 of first dose cycle
Number of patients with dose limiting toxicities defined as adverse events (AE) or laboratory abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) version 4.03 ≥ Grade 3 that are not clearly related to disease progression
3 secondary outcomes
Tumor response
Time frame: Weeks 4, 12, 20 and 28
Changes in vital signs, physical examination or clinical laboratory from baseline
Time frame: Weeks 4, 8, 12, 16, 20, 24 and 28
Number of patients with ophthalmological changes from baseline
Time frame: Weeks 4, 16 and 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2016.
- Individual participant dataSharing planned: No. Phase 1 pharmacology study
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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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SNX-5422 in people with Cancer, run by Esanex Inc. at 2 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 18 inclusion and 19 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: finished, as of the sponsor's last update on 16 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients with dose limiting toxicities (time frame: Day 28 of first dose cycle). 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 16 Aug 2016.