NCT00526045

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
117

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline
Completed

Started Jul 2007

Typical duration for phase_1 breast-cancer

Geographic Reach
4 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2007

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

September 5, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 6, 2007

Completed
4.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2012

Completed
Last Updated

December 17, 2020

Status Verified

May 1, 2013

Enrollment Period

4.8 years

First QC Date

September 5, 2007

Last Update Submit

December 11, 2020

Conditions

Breast CancerHematologic Neoplasms

Keywords

AUY922Solid tumorsBreast CancerPhase I/IIAdvanced Solid malignancies (Phase I)Breast Cancer ( Phase II )HER2+ER+HSP90

Outcome Measures

Primary Outcomes (1)

  • The safe dose of AUY922 when administered once a week

    54 weeks (MTD determination)

Secondary Outcomes (2)

  • Efficacy of AUY922 administered once a week

    Baseline, and every 2 cycles (time to document tumor progression)

  • Pharmacokinetics of AUY922 and Pharmacodynamics by PET response, blood and tumor biomarkers at baseline and post-AUY922

    Baseline and every 2 cycles

Study Arms (3)

Escalation

EXPERIMENTAL
Drug: AUY922 2 mg/m2

HER2 Positive

EXPERIMENTAL
Drug: AUY922 2 mg/m2

ER+ breast cancer

EXPERIMENTAL
Drug: AUY922 2 mg/m2

Interventions

AUY922 2 mg/m2DRUG
ER+ breast cancerEscalationHER2 Positive

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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.
  • 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.
  • All patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression.
  • All patients must have progressive disease before entering the study
  • Age ≥ 18 years.
  • World Health Organization (WHO) Performance Status of ≤ 2.
  • Life expectancy of ≥ 12 weeks.
  • +1 more criteria

You may not qualify if:

  • 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
  • Prior treatment with any HSP90 or HDAC inhibitor compound.
  • 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)
  • Patients who have not recovered from side effects of previous systemic anticancer therapy to less than grade 2 CTCAE prior to the first dose.
  • Pregnant or lactating women.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

UCLA/ University of California Los Angeles UCLA

Los Angeles, California, 90095, United States

Location

Georgia Health Sciences University Med College of GA

Augusta, Georgia, 30912, United States

Location

Dana Farber Cancer Institute StudyCoordinator:CAUY922A2101

Boston, Massachusetts, 02115, United States

Location

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

St Louis, Missouri, 63110, United States

Location

Nevada Cancer Institute Clinical Trials Office

Las Vegas, Nevada, 89135, United States

Location

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

Houston, Texas, 77030-4009, United States

Location

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

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Bellinzona, 6500, Switzerland

Location

Novartis Investigative Site

Sutton, SM2 5PT, United Kingdom

Location

Related Links

MeSH Terms

Conditions

Breast NeoplasmsHematologic Neoplasms

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 5, 2007

First Posted

September 6, 2007

Study Start

July 1, 2007

Primary Completion

April 1, 2012

Study Completion

April 1, 2012

Last Updated

December 17, 2020

Record last verified: 2013-05

Locations

CH(1)GB(1)NL(1)US(7)