Hsp90 Inhibitor AUY922 in Treating Older Patients With Advanced Solid Malignancies

• Status: Terminated
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial studies the side effects and best dose of Hsp90 inhibitor AUY922 in treating older patients with advanced solid malignancies. Hsp90 inhibitor AUY922 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dale Shepard, MD, PhD
• Collaborator: National Cancer Institute (NCI)

Criteria

Inclusion Criteria:

• Patients must have a histologically proven solid tumor malignancy which is refractory to standard therapy and for which no curative therapy is available

• Patients must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST); irradiated lesions are only evaluable for disease progression

• Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 1

• Life expectancy of >= 12 weeks

• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

• Hemoglobin (Hgb) >= 9 g/dl

• Platelets (plt) >= 100 x 10^9/L

• Potassium within normal limits or correctable with supplements

• Total calcium (corrected for serum albumin) and phosphorus within normal limits

• Magnesium above lower limit of normal (LLN) or correctable with supplements

• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) if no liver metastases are present

• AST/SGOT and ALT/SGPT =< 5 x ULN if liver metastases are present

• Serum bilirubin =< 1.5 x ULN

• Serum creatinine =< 1.5 x ULN or 24-hour clearance >= 50 ml/min

• Patients must be able to understand and voluntarily sign written informed consent

Male participants with partners who are of child bearing potential must:

• Agree to use double barrier method of birth control 28 days prior to study entry, during course of study and for 28 days following the last dose of AUY922

• OR have history of a vasectomy

Exclusion Criteria:

Patients with central nervous system (CNS) metastasis which are:

• Symptomatic or

• Require treatment for symptom control and/or

• Growing Note: Patients without clinical signs or symptoms of CNS involvement are not required to have a computed tomography (CT)/magnetic resonance imaging (MRI) of the brain

• Prior treatment with any heat shock protein (HSP)90 or histone deacetylase (HDAC) inhibitor compounds

Patients who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames:

• Radiotherapy or conventional chemotherapy: within 4 weeks

• Palliative radiotherapy: within 2 weeks

• Nitrosoureas, mitomycin, or monoclonal antibodies, such as trastuzumab, within 6 weeks

• Any systemic anti-cancer treatment for which the elimination period is not known, or investigational drugs (i.e. targeted agents) within a duration of =< 5 half lives of the agent and their active metabolites (if any)

• Treatment with therapeutic doses of coumadin-type anticoagulants (maximum daily dose of 2 mg, for line patency permitted)

• Unresolved diarrhea >= Common Terminology Criteria for Adverse Events (CTCAE) grade 1, despite treatment with antidiarrheal agents

• Patients with malignant ascites that require invasive treatment

• Male patients whose partners are women of child-bearing potential (WCBP) not using double-barrier methods of contraception

• Acute or chronic liver or renal disease

• Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol

• Major surgery =< 2 weeks prior to Cycle 1, Day 1 or who have not recovered from such therapy; (placement of a venous access device within 2 weeks is permitted)

Impaired cardiac function, including any one of the following:

• History (or family history) of long QT syndrome

• Mean corrected QT interval (QTc) >= 450 msec on baseline electrocardiogram (ECG)

• History of clinically manifested ischemic heart disease =< 6 months prior to study start

• History of heart failure or left ventricular (LV) dysfunction (left ventricular ejection fraction [LVEF] =< 45%) by multigated acquisition scan (MUGA) or echocardiogram (ECHO)

• Clinically significant ECG abnormalities including 1 or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB); ST segment elevation or depression > 1mm, or 2nd (Mobitz II), or 3rd degree atrioventricular (AV) block

• History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes

• Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)

• Clinically significant resting bradycardia (< 50 beats per minute)

• Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the corrected QT using Bazett's formula (QTcB) interval or inducing Torsades de Pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY922

• Patients who are dependent on a pacemaker due to cardiac conduction dysfunction; known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)

• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention

• Patients unwilling or unable to comply with the protocol