Safety and Pharmacology of SNX-5422 Plus Carboplatin and Paclitaxel in Subjects With Solid Tumors

NCT01892046 | Completed Phase 1

• 1 other identifier: SNX5422-CLN1-006
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 4

Brief Summary

Heat shock protein 90 (Hsp90) is a chemical in the body that is involve in the promotion of cancer. SNX-5422 is an experimental drug that blocks Hsp90.

Conditions

Cancer

Keywords

Small Cell Lung Cancer; Non Small Cell Lung Cancer; 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 after commencing study treatment that are not clearly related to disease progression

  First 28 day cycle

Secondary Outcomes (3)

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

  Day 28 of each cycle

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

  Day 28 of each cycle

• Tumor response

  Every 12 weeks

Study Arms (1)

SNX-5422

EXPERIMENTAL

Open label administration of SNX-5422 capsules every other day (QOD) for 21 days of a 28 day cycle. Dose escalation will be based on safety outcomes defined as 1 or less dose limiting toxicities during the first 28 day cycle at any dose level. During the dose escalation phase, subjects will receive carboplatin and paclitaxel once every 21 days for a total of 4 courses. During the maintenance phase, SNX-5422 at the MTD will be dosed every other day (QOD) for 21 days of a 28 day cycle.

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. Maintenance doses at the maximum tolerated dose.

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.
• Pathologic evidence of Small Cell Lung Cancer, or Non-Small Cell Lung Cancer.
• No more than one prior line of antitumor therapy for metastatic disease, excluding prior treatment with tyrosine kinase inhibitors. An interval of at least 1 week is required for washout of the tyrosine kinase inhibitor.
• Measurable disease using RECIST criteria (version 1.1).
• Life expectancy of at least 3 months.
• 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) ≤2.0 x ULN except in subjects with known hepatic metastasis, where AST or ALT can be ≤5.0 x ULN.
• Hemoglobin ≥9 mg/dL.
• Estimated creatinine clearance of ≥40 mL/min
• Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia.
• Signed informed consent form (ICF)

You may not qualify if:

• CNS metastases that are symptomatic and /or requiring steroids.
• Prior treatment with any Hsp90 inhibitor.
• Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
• 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 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.
• Treatment with other anticancer drugs within 28 days or 5 half-lives of anticancer therapy (whichever is shorter), and treatment with any other investigational agent is prohibited from 30 days prior to the first dose of SNX-5422 and throughout the study.

Sponsors & Collaborators

• Esanex Inc.: lead

Study Sites (4)

Georgetown University Medical Center

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

Location

Georgia Regents University Cancer Center

Augusta, Georgia, 30912, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung

Interventions

SNX-5422

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

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: June 30, 2013
• First Posted: July 3, 2013
• Study Start: November 1, 2013
• Primary Completion: February 1, 2017
• Study Completion: July 1, 2017
• Last Updated: July 26, 2017

Record last verified: 2017-07

Locations

US (4)