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A Phase I Dose Escalation, Multi-center, Open-label Study of AUY922 Administered IV on a Once Weekly Schedule in Adult Patients With Advanced Solid Malignancies Including Phase II Expansion Arms in Patients With Either HER2 Positive or ER Positive Locally Advanced or Metastatic Breast Cancer.


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer, Hematologic Neoplasms

Thank you

Trial Information

A Phase I Dose Escalation, Multi-center, Open-label Study of AUY922 Administered IV on a Once Weekly Schedule in Adult Patients With Advanced Solid Malignancies Including Phase II Expansion Arms in Patients With Either HER2 Positive or ER Positive Locally Advanced or Metastatic Breast Cancer.


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.

6. Cardia exclusion criteria:

- 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.

9. Cardiac exclusion criteria:

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.

Other protocol-defined inclusion/exclusion criteria may apply

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The safe dose of AUY922 when administered once a week

Outcome Time Frame:

54 weeks (MTD determination)

Safety Issue:

Yes

Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals

Authority:

United States: Food and Drug Administration

Study ID:

CAUY922A2101

NCT ID:

NCT00526045

Start Date:

July 2007

Completion Date:

April 2012

Related Keywords:

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

Name

Location

UCLA/ University of California Los Angeles UCLALos Angeles, California  90095
Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3)San Antonio, Texas  78229
Georgia Health Sciences University Med College of GAAugusta, Georgia  30912
Dana Farber Cancer Institute StudyCoordinator:CAUY922A2101Boston, Massachusetts  02115
Washington University School Of Medicine-Siteman Cancer Ctr Dept. of Siteman Cancer Ctr.St. Louis, Missouri  63110
Nevada Cancer Institute Clinical Trials OfficeLas Vegas, Nevada  89135
MD Anderson Cancer Center/University of Texas Thoractic Head/Neck Med.Onc(2)Houston, Texas  77030-4009