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

NCT02063958 | Completed Phase 1

• 1 other identifier: SNX5422-CLN-009
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Cancer

Keywords

Neuroendocrine tumor; Hsp90

Outcome Measures

Primary Outcomes (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.

  First 28 day cycle

Secondary Outcomes (3)

• Number of patients with adverse events as a measure of tolerability

  Every 4 weeks

• Changes in ECG, vital signs, laboratory or physical examination

  Every 4 weeks

• Tumor response

  Every 8 weeks

Study Arms (1)

SNX-5422

EXPERIMENTAL

Open-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.

Drug: SNX-5422

Interventions

SNX-5422 DRUG

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.

SNX-5422

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Esanex Inc.: lead

Study Sites (5)

Mayo Clinic

Scottsdale, Arizona, 85259-5499, United States

Location

Stanford Medicine

Stanford, California, 94305, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Center for Cancer Research, National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Neoplasms; Neuroendocrine Tumors

Interventions

SNX-5422

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: February 17, 2014
• Study Start: February 1, 2014
• Primary Completion: March 27, 2017
• Study Completion: March 20, 2018
• Last Updated: July 30, 2018

Record last verified: 2018-07

Locations

US (5)