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Protocol Details

A Phase 1, Open-Label, Dose-Escalation Study of SNX-5422 and Everolimus in Subjects with Neuroendocrine Tumors

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18
Max Age: 100

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Small-Molecule Inhibitor;
Molecular Chaperone;
Heat Shock Protein 90 (Hsp90);
Client Protein Level

Recruitment Keyword(s)



Neuroendocrine Tumor;

Investigational Drug(s)


Investigational Device(s)



Drug: SNX-5422
Drug: Everolimus

Supporting Site

National Cancer Institute


- Neuroendocrine tumors come from cells in the endocrine (hormonal) and nervous systems. Renal cell carcinoma is a type of kidney cancer in adults. Researchers want to see if a drug called SNX-5422, when given with the drug everolimus, might be able to help people with these diseases.


- To determine the highest tolerable dose of SNX-5422 that can be given with everolimus. To determine if this combination will cause tumor cells to shrink or disappear.


- Adults 18 years or older who have been diagnosed with a neuroendocrine or renal cell tumor.


- Participants will be screened with a medical history, physical exam with vital signs, and blood and urine tests. They will have an electrocardiogram (ECG) of heart electrical activity and an eye exam. A tumor sample may be taken.

- Participants will have a physical exam and blood and urine tests. They will get one SNX-5422 capsule and one everolimus capsule.

- Treatment will follow a 28-day cycle:

- Participants will take SNX-5422 at home every other day for 21 days, then none for 7 days.

- They will take everolimus for 28 days.

- They will have weekly study visits. These may include physical exam, ECG, eye exam, and blood and urine samples. Tumor size may be measured.

- After Cycle 6, there will be only 1 visit per cycle.

- Participants will have a final study visit after finishing the study drug. They will have a physical exam, eye exam, and ECG. Blood and urine will be collected. They will have imaging tests and scans of their tumor.

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For a subject to be eligible for participation in this study, all of the following criteria must apply:

-Males or non-pregnant, non-breastfeeding females 18 years-of-age or older.

-Archived tumor sample or biopsy sample (will also be used for genetic testing as part of validation of a biomarker)

-Pathologic evidence of one of the following cancers:

--locally advanced or metastatic neuroendocrine tumor of gastro-enteropancreatic, pulmonary (other than small cell lung cancer), or thymic origin with no more than 4 prior lines of systemic anti-cancer therapy.

-Measurable (RECIST) indicator lesion not previously irradiated.

-Life expectancy of at least 3 months.

-Karnofsky performance score greater than or equal to 70.

-Adequate baseline laboratory assessments, including

--Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10(9)/L.

--WBC >3000/microliter

--Platelet count of greater than or equal to 100 x 109/L.

--Total bilirubin level less than or equal to 1.5 times institutional upper limit of normal (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 2 x ULN except in subjects with known hepatic metastasis, where AST or ALT

can be greater than or equal to 5.0 x ULN.

--Hemoglobin greater than or equal to 9 g/dL.

--Creatinine <1.5 X upper limit of normal or estimated plasma creatinine

clearance of greater than or equal to 40 mL/min (using the Cockroft-Gault equation):

---CLcreat = (140 - age) x body mass [x 0.85 if female]) / 72 x creatinine, where age is given in years, body mass is given in kg, and creatinine is given in mg/dL.

-Signed informed consent form (ICF) indicating that the subject has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.

-Recovered from toxicities of previous anticancer therapy to CTCAE Grade less than or equal to 1 with the exception of alopecia.

-Subjects with reproductive capability must agree to practice adequate contraception methods. Males must be surgically sterilized or be willing to use condoms from the first dose of study drug until at least 30 days after the last dose. Females must be surgically sterilized, post-menopausal for at least 1 year, or willing to use an appropriate double barrier method or oral, patch, implant, or injectable contraception from the first dose of study drug until at least 30 days after the last dose.

-Adequate venous access.


A subject will not be eligible for participation in this study if any of the following criteria apply:

-Subjects in whom everolimus is contraindicated.

-Subjects with clinically significant interstitial lung disease, or obstructive disease without sufficient reserve (Forced Expiratory Volume in one second less than 50% of predicted).

- Neuroendocrine tumor with uncontrolled hormone related symptoms, particularly those symptoms that may mimic toxicity of SNX-5422 such as diarrhea (diarrhea greater than or equal to 4 stools per day).

- Neuroendocrine cancer of the thyroid.

-Prior treatment with any Hsp90 inhibitor.

-Prior failed treatment with mTOR inhibitors (current use of everolimus is allowed if subject is still having benefit from treatment with everolimus).

-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.

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Not Provided

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Principal Investigator

Referral Contact

For more information:

Arun Rajan, M.D.
National Cancer Institute (NCI)
NIHBC 10 - CRC BG RM 4-5330D
(240) 760-6236

Corrine M. Keen, R.N.
National Cancer Institute (NCI)
National Institutes of Health
Building 10
Room 8D44B
10 Center Drive
Bethesda, Maryland 20892
(240) 760-6097

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office

Clinical Trials Number:


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