Phase I-II Study to Determine the Maximum Tolerated Dose (MTD) of AUY922 in Advanced Solid Malignancies, and Efficacy in HER2+ or ER+ Locally Advanced or Metastatic Breast Cancer Patients

NCT ID: NCT00526045

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

117 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-07-31

Study Completion Date

2012-04-30

Brief Summary

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This is a phase I/II, open-label, multicenter study of AUY922 administered intravenously in patients with advanced solid malignancies to determine the maximum tolerated dose. Phase II expansion arms will investigate efficacy in patients with either HER2 positive or ER positive locally advanced or metastatic breast cancer. Additional patients with advanced solid malignancies will also be investigated in a separate expansion arm. Safety, pharmacokinetics and pharmacodynamics will be assessed.

Detailed Description

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Conditions

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Breast Cancer Hematologic Neoplasms

Keywords

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AUY922 Solid tumors Breast Cancer Phase I/II Advanced Solid malignancies (Phase I) Breast Cancer ( Phase II ) HER2+ ER+ HSP90

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Escalation

Group Type EXPERIMENTAL

AUY922 2 mg/m2

Intervention Type DRUG

HER2 Positive

Group Type EXPERIMENTAL

AUY922 2 mg/m2

Intervention Type DRUG

ER+ breast cancer

Group Type EXPERIMENTAL

AUY922 2 mg/m2

Intervention Type DRUG

Interventions

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AUY922 2 mg/m2

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Dose-escalation and MTD dose expansion arm: Patients with histologically confirmed, advanced malignant solid tumors whose disease has progressed on standard therapy or for whom no standard therapy exists.

Breast cancer phase II expansion arms only:
1. Females patients with HER2 positive non-operable locally advanced or metastatic breast cancer must have:

* History of trastuzumab resistance, defined as either local or systemic disease progression on treatment with at least 8 weeks of a trastuzumab containing regimen.
* Received up to 3 prior anti HER2 based regimens (i.e. trastuzumab and/or lapatinib in combination with other agents) for metastatic disease
* Patients who develop metastases while receiving adjuvant or neo-adjuvant trastuzumab are eligible.

HER2 positive patients, tumor/s must demonstrate HER2 over-expression based on either:
* Immunohistochemistry (IHC) at the 3+ level, or
* IHC 2+ confirmed by fluorescence in-situ hybridization (FISH). Tumors tested by FISH must be positive by the specific FISH assay for the amplification of HER2.
2. Female patients with ER positive non-operable locally advanced or metastatic breast cancer patients who received standard sequence lines of endocrine therapy and whose disease has progressed on at least one and up to 3 lines of endocrine and/or cytotoxic therapy for advanced disease.
2. All patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression.
3. All patients must have progressive disease before entering the study
4. Age ≥ 18 years.
5. World Health Organization (WHO) Performance Status of ≤ 2.
6. Life expectancy of ≥ 12 weeks.
7. Absolute Neutrophil Count (ANC) 1.5 x 109/L; hemoglobin (Hgb) 9 g/dl; platelets (plt) 100 x 109/L; potassium, calcium, magnesium and phosphorus within normal limits or correctable with supplements; AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present; serum bilirubin 1.5 x ULN; serum albumin \> 2.5g/dl and serum creatinine 1.5 x ULN or 24-hour clearance 50 ml/min

Exclusion Criteria

1. Patients with 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 CT/MRI of the brain
2. Prior treatment with any HSP90 or HDAC inhibitor compound.
3. Patient who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames:

* Chemotherapy within 4 weeks
* Radiotherapy within 4 weeks
* Palliative radiotherapy: within 2 weeks
* Trastuzumab treatment within 4 weeks
* Nitrosoureas, mitomycin and monoclonal antibodies (except trastuzumab): within 6 weeks
* Any continuous-dosing (i.e. daily dosing, every-other-day dosing, Monday- Wednesday-Friday dosing, weekly etc) of systemic anticancer treatment for which the recovery 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)
4. Patients who have not recovered from side effects of previous systemic anticancer therapy to less than grade 2 CTCAE prior to the first dose.
5. Pregnant or lactating women.

* History (or family history) of long QT syndrome.
* Mean QTc ≥ 450 msec on screening ECG
* History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina, coronary arteriography or cardiac stress testing/imaging with findings consistent with coronary occlusion or infarction, ≤ 6 months prior to study start.
* History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO
7. Known diagnosis of HIV infection (HIV testing is not mandatory).
8. Acute or chronic liver disease, acute or chronic renal disease or other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.

Mean QTc ≥ 450 msec on screening ECG and clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevations or depressions \> 1mm, or 2nd (Mobitz II) or 3rd degree AV block; clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevations or depressions \> 1mm, or 2nd (Mobitz II) or 3rd degree AV block.

History (or family history) of long QT syndrome, heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO, history of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina, coronary arteriography or cardiac stress testing/imaging with findings consistent with coronary occlusion or infarction, ≤ 6 months prior to study start; history or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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UCLA/ University of California Los Angeles UCLA

Los Angeles, California, United States

Site Status

Georgia Health Sciences University Med College of GA

Augusta, Georgia, United States

Site Status

Dana Farber Cancer Institute StudyCoordinator:CAUY922A2101

Boston, Massachusetts, United States

Site Status

Washington University School Of Medicine-Siteman Cancer Ctr Dept. of Siteman Cancer Ctr.

St Louis, Missouri, United States

Site Status

Nevada Cancer Institute Clinical Trials Office

Las Vegas, Nevada, United States

Site Status

MD Anderson Cancer Center/University of Texas Thoractic Head/Neck Med.Onc(2)

Houston, Texas, United States

Site Status

Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3)

San Antonio, Texas, United States

Site Status

Novartis Investigative Site

Groningen, , Netherlands

Site Status

Novartis Investigative Site

Bellinzona, , Switzerland

Site Status

Novartis Investigative Site

Sutton, , United Kingdom

Site Status

Countries

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United States Netherlands Switzerland United Kingdom

Related Links

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https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=8324

Resutls for CAUY922A2101 on the Novartis clinical trials website

Other Identifiers

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2006-002766-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAUY922A2101

Identifier Type: -

Identifier Source: org_study_id