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CancerPhase 1NCT02063958

Safety and Pharmacology of SNX-5422 Plus Everolimus in Subjects With Neuroendocrine Tumors

A Phase 1 study testing SNX-5422 in people with Cancer, run by Esanex Inc. at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus. 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
19 participants
Where
5 sitesUnited States
Study dates
Feb 2014to 20 Mar 2018
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.
  • Archived neuroendocrine tumor sample or biopsy sample (will also be used for genetic testing).
  • Pathologic evidence of chemo-resistant Small Cell Lung cancer (relapse <90 days after 1st line), chemo-sensitive Small Cell Lung Cancer (relapse >90 days after first line), locally advanced metastatic neuroendocrine tumor of gastro-entero, pancreatic, pulmonary (other than Small Cell Lung) or thymic origin, or advanced renal cell carcinoma for which everolimus is indicated.
  • Measurable (RECIST) indicator lesion not previously irradiated.
  • Life expectancy of at least 3 months.
  • No more than 4 prior lines of systemic anti-cancer therapy.
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  • 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 or aspartate aminotransferase ≤2 x ULN
  • Hemoglobin ≥9 mg/dL.
  • Creatinine <1.5 X upper limit of normal or estimated plasma creatinine clearance of ≥40 mL/min
  • Signed informed consent form
  • Recovered from toxicities of previous anticancer therapy
  • Subjects with reproductive capability must agree to practice adequate contraception methods.

Who cannot join

  • Subjects in whom everolimus is contraindicated.
  • Subjects with clinically significant interstitial lung disease, or obstructive disease without sufficient reserve
  • Carcinoid with hormone related symptoms
  • Neuroendocrine cancer of the thyroid or thymus.
  • Rare pancreatic neuroendocrine cancers such as, insulinomas, glucagonomas, gastrinomas.
  • Prior treatment with any Hsp90 inhibitor.
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  • Prior failed treatment with mTOR inhibitors
  • CNS metastases that are symptomatic and /or requiring escalating doses of steroids.
  • Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
  • Conventional chemotherapy or radiation within 4 weeks.
  • 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.
  • 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 appropriate 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

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Center for Cancer Research, National Cancer Institute

    Bethesda, Maryland, 20892

  • hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Mayo Clinic

    Scottsdale, Arizona, 85259-5499

  • Stanford Medicine

    Stanford, California, 94305

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase 1, Open-label, Dose-escalation Study of SNX 5422 and Everolimus in Subjects With Neuroendocrine Tumors.

Study is designed to determine the maximum tolerated dose (MTD) of SNX-5422 when given in combination with everolimus.

Read the detailed description

Heat shock protein 90 (Hsp90) plays a central role in the maturation and maintenance of numerous proteins, for example HER2 and mutated EGFR, that are critical for tumor cell viability and growth; 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). Hsp90 has been found to be expressed in 95% of subjects with pancreatic neuroendocrine tumors.

This study will determine the MTD of SNX-5422 when given in combination with everolimus in patients with neuroendocrine tumors.The clinical starting dose of 50 mg/m2 qod for SNX-5422 in combination with daily everolimus is 50% of the SNX-5422 qod mono-therapy MTD. The choice to continue once every other day SNX-5422 dosing is based on the safety and efficacy profiles from prior studies, so that drug holidays are interspersed into weekly dosing. The planned subsequent dose levels are 75% and 100% of the SNX-5422 qod mono-therapy MTD.

Conditions
Cancer
Being tested
SNX-5422
Keywords
Neuroendocrine tumor, Hsp90
Medical subject headings
Neoplasms, Neuroendocrine Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SNX-5422Drug

    Capsule dosed every other day for 21 days out of a 28 day cycle. Dose escalation based on safety not to exceed a dose of 100 mg/m2. Maintenance therapy of SNX-5422 at the MTD will be allowed for all patients not experiencing significant toxicity.

Study groups in NCT02063958
Study groupRoleWhat they receive
SNX-5422ExperimentalOpen-label administration of SNX-5422 capsules dosed in the morning once every other day (qod) for 21 days (11 doses), followed by a 7 day drug free period. Dose escalation will be based on safety defined as 1 or less dose limiting toxicities during the first 28 day cycle at any dose level. Dose escalation will not exceed a dose of 100 mg/m2 SNX-5422 qod even if the MTD has not been identified. Subjects will receive daily oral everolimus in the PM about the same time every day for 28 days.
Receives: Drug: SNX-5422

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of patients with dose limiting toxicities

    Number of patients with dose limiting toxicities defined as adverse events or laboratory abnormalities of Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 ≥ Grade 3 that are not clearly related to disease progression or delay by more than 4 weeks in receiving the next scheduled cycle due to persisting toxicities and attributable to the combination of SNX-5422 and everolimus despite optimal medical supportive management.

    Measured: First 28 day cycle

Secondary outcomes (3)

  1. Number of patients with adverse events as a measure of tolerability

    Frequency and severity of adverse events

    Measured: Every 4 weeks

  2. Changes in ECG, vital signs, laboratory or physical examination

    Changes in ECG, vital signs, laboratory or physical examination from baseline

    Measured: Every 4 weeks

  3. Tumor response

    Measurements from tumor imaging within 1 month prior to the screening visit will be used as the baseline assessment. This assessment will be performed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Follow-up imaging of known sites of the disease, preferably by CT scan, will be performed at intervals appropriate to the subject's disease and clinical findings.

    Measured: Every 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Feb 2014 (estimated)
  2. Study startFeb 2014
  3. Primary completion27 Mar 2017
  4. Study completion20 Mar 2018

Resources

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
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02063958
Sponsor's protocol ID
SNX5422-CLN-009
Status last verified
Jul 2018
First submitted
13 Feb 2014
Last updated
30 Jul 2018
Results posted
No
Data monitoring committee
No

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 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 17 inclusion and 26 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 30 Jul 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 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: First 28 day cycle). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02063958.

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 30 Jul 2018.

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