Hsp90 Inhibitor AUY922 in Treating Older Patients With Advanced Solid Malignancies

NCT01602627 | Terminated Phase 1 DMC

• 2 other identifiers: CASE3Y10NCI-2011-03107
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (1)

• MTD of Hsp90 inhibitor AUY922

  A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as clinically relevant, and occurs \< 28 days following the first dose of AUY922. Toxicity will be measured by CTCAE criteria (Version 4.02). The MTD will be determined using a standard design.

  at 28 days

Secondary Outcomes (8)

• Toxicity by CTCAE (v 4.02)

  at 28 days

• Pharmacokinetic parameters, including area under the curve (AUC), clearance, volume of distribution (VD), time to the maximum concentration (Tmax), maximum plasma concentration (Cmax), and elimination half-life

  at baseline and at 28 days (first cycle)

• Tumor response will be measured by RECIST criteria (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD], overall response [OR], response rate [RR])

  at baseline and at end of cycle 2 (8 weeks)

• Geriatric assessment will be made including Mini Mental Exam, Get up and Go, assessment of comorbidity, and Geriatric Depression Scale

  at baseline and at end of cycle 2 (8 weeks)

• Evaluation of responses to a bioethics questionnaire will be used to assess patient factors influencing enrollment in this elderly-specific phase I trial

  Baseline

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

Patients receive Hsp90 inhibitor AUY922 IV over 1 hour on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Hsp90 inhibitor AUY922; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

Hsp90 inhibitor AUY922 DRUG

Given IV

Also known as: AUY922

Treatment (enzyme inhibitor therapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (enzyme inhibitor therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dale Shepard, MD, PhD: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide

Study Officials

• Dale Shepard

  Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 16, 2012
• First Posted: May 21, 2012
• Study Start: September 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2012
• Last Updated: February 7, 2013

Record last verified: 2013-02

Locations

US (1)