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

Cancer Clinical Trial

Official title:

A Phase 1, Open-label, Dose-escalation Study of SNX 5422 Plus Carboplatin and Paclitaxel in Subjects With Selected Solid Tumors.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01892046
• Other study ID #: SNX5422-CLN1-006
• Status: Completed
• Phase: Phase 1
• First received: June 30, 2013
• Last updated: July 25, 2017
• Start date: November 2013
• Est. completion date: July 2017

Study information

• Verified date: July 2017
• Source: Esanex Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Heat shock protein 90 (Hsp90) chaperone proteins stabilize well over 200 different known client proteins helping them to fold correctly as they take up their rightful positions in the cell. Inhibitors of the chaperone protein Hsp90 are of current interest because of the central role of Hsp90 in the maturation and maintenance of numerous proteins 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). The study will determine the maximum tolerated dose (MTD) of SNX-5422 when combined with carboplatin plus paclitaxel in selected solid tumors and assess the safety and efficacy of SNX-5422 alone dosed at the MTD as maintenance therapy in selected solid tumors treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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)

• Subjects with reproductive capability must agree to practice adequate contraception methods.

• Adequate venous access

Exclusion Criteria:

• 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.

• Radiation treatment within 2 weeks.

• 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.

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• SNX-5422
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.

Locations

Country	Name	City	State
United States	Georgia Regents University Cancer Center	Augusta	Georgia
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Georgetown University Medical Center	Washington, D.C.	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Esanex Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of patients with adverse events as a measure of tolerability	Frequency and severity of adverse events	Day 28 of each cycle
Secondary	Changes in ECG, vital signs, laboratory or physical examination	Changes in ECG, vital signs pr physical or laboratory examinations from baseline	Day 28 of each cycle
Secondary	Tumor response	Tumor response using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (version 1.0) assessed by CT scan (or MRI) when combined with carboplatin and paclitaxel and for SNX-5422 when given alone during the maintenance part.	Every 12 weeks