Safety and Pharmacology Study of SNX-5422 in Subjects With Resistant Lung Adenocarcinoma

NCT01851096 | Completed Phase 1

• 1 other identifier: SNX-5422-CLN1-007
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Cancer

Keywords

Hsp90; SNX-5422; Erlotinib; Lung adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Number of patients with dose limiting toxicities

  Number of patients with dose limiting toxicities defined as adverse events (AE) or laboratory abnormalities of Common Terminology Criteria for Adverse Events(CTCAE) version 4.03 ≥ Grade 3 that are not clearly related to disease progression

  Day 28 of first dose cycle

Secondary Outcomes (3)

• Tumor response

  Weeks 4, 12, 20 and 28

• Changes in vital signs, physical examination or clinical laboratory from baseline

  Weeks 4, 8, 12, 16, 20, 24 and 28

• Number of patients with ophthalmological changes from baseline

  Weeks 4, 16 and 28

Study Arms (1)

SNX-5422

EXPERIMENTAL

Open label administration of SNX-5422 tablets every other day for 21 days on a 28 day cycle. Dose escalation of SNX-5422 based on safety outcomes

Drug: SNX-5422

Interventions

SNX-5422 DRUG

Capsules dosed every other day in the morning starting at a dose of 50 mg/m2. Dose escalation based on safety. Subjects will also receive 150 mg erlotinib daily (in the afternoon).

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.
• Received treatment with erlotinib/gefitinib throughout the one month prior to enrollment and at least six months at any time.
• Must have undergone a biopsy after the development of acquired resistance.
• Pathologic evidence of advanced lung adenocarcinoma (stage IIIB or stage IV) confirmed histologically/cytologically
• Radiographic progression by RECIST during treatment with erlotinib/gefitinib.
• Measurable (RECIST) indicator lesion not previously irradiated.
• No more than 4 prior lines of cytotoxic chemotherapy, including erlotinib/gefitinib
• 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) ≤1.5 x ULN.
• Hemoglobin ≥9 mg/dL.
• Creatinine \<1.5 X upper limit of normal or estimated plasma creatinine clearance of ≥40 mL/min (using the Cockroft-Gault equation)

You may not qualify if:

• CNS metastases which are symptomatic and /or requiring escalating doses of steroids.
• Prior treatment with any Hsp90 inhibitor.
• Conventional chemotherapy, radiation or monoclonal antibodies within 4 weeks (erlotinib/gefitinib therapy within the past 4 weeks IS allowed).
• 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 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.

Sponsors & Collaborators

• Esanex Inc.: lead

Study Sites (2)

Georgetown University Medical Center

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

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Neoplasms; Adenocarcinoma of Lung

Interventions

SNX-5422

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site

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: May 4, 2013
• First Posted: May 10, 2013
• Study Start: March 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: August 1, 2016
• Last Updated: August 16, 2016

Record last verified: 2016-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)