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A Phase 2, Open-Label, Single-Arm, Multicenter, Multinational Study to Evaluate the Antitumor Activity and Safety of IPI-504, A Novel Small Molecule Inhibitor of Heat Shock Protein 90(HSP90), in Patients With Locally Advanced or Metastatic Human Epidermal Growth Factor Receptor 2-Positive(HER2+) Breast Cancer That Has Progressed Despite Prior Her2=Targeted Therapy


Phase 1/Phase 2
18 Years
80 Years
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

A Phase 2, Open-Label, Single-Arm, Multicenter, Multinational Study to Evaluate the Antitumor Activity and Safety of IPI-504, A Novel Small Molecule Inhibitor of Heat Shock Protein 90(HSP90), in Patients With Locally Advanced or Metastatic Human Epidermal Growth Factor Receptor 2-Positive(HER2+) Breast Cancer That Has Progressed Despite Prior Her2=Targeted Therapy


To evaluate the antitumor activity following treatment with IPI-504 in patients with locally
advanced or metastatic HER2+ breast cancer that has progressed despite prior HER2-targeted
therapy.


Inclusion Criteria:



- Adult women at least 18 years of age at the time of signing the Informed Consent
Form;

- Written informed consent and HIPAA authorization (applies to covered entities in the
USA only) obtained from the patient prior to performing any study-related procedures,
including screening visits;

- Pathologically confirmed breast cancer from assessment of primary or metastatic
breast cancer;

- Locally advanced or metastatic breast cancer as defined as a T4 primary tumor and
Stage IIIB/ IIIC disease or Stage IV disease, respectively, according to the Sixth
Edition of the American Joint Committee on Cancer [AJCC] TNM System (Appendix A);

- Measurable disease according to RECIST - lesions that can be accurately measured in
at least one dimension with longest diameter ³ 20 mm using conventional computed
tomography (CT) or magnetic resonance imaging (MRI) scan or ³ 10 mm with spiral CT
scan; the use of chest x-ray is not encouraged, however, it may be used if necessary;

- HER2-expressing primary or metastatic tumor (Grade 3+ staining intensity [on a scale
of 0 to 3] via IHC assays or HER2 amplification on fluorescence in situ
hybridization), with results of the most recent biopsy taken as indicative of HER2
status;

- Progression after treatment with at least 1 but not more than 3 regimens containing
trastuzumab or lapatinib (treatment regimens that do not include trastuzumab or
lapatinib do not qualify) for adjuvant, neoadjuvant, locally advanced, or metastatic
disease with either one of the following stipulations:

1. Patients may have received neoadjuvant or adjuvant treatment with prior
trastuzumab or lapatinib treatment but must have demonstrated no evidence of
disease progression for >12 months following completion of therapy;

2. Patients have received a trastuzumab-based therapy for locally advanced or
metastatic disease for a minimum of 9 weeks duration. Patients may have
received more than 1 trastuzumab-based combination therapy; Patients have
received a lapatinib-based therapy for locally advanced or metastatic diseases
for a minimum of 9 weeks duration;

- Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical
procedures to NCI CTCAE Grade ≤ 1 or patient's baseline;

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (see Appendix
B);

- Life expectancy of at least 3 months;

- Left ventricular ejection fraction > 45%;

- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; platelet count ≥ 100,000
cells/mm3; hemoglobin ≥ 9.0 g/dL (may be increased to this level with transfusion as
long as there is no evidence of active bleeding);

- Prothrombin time or international normalized ratio within normal range (unless a
patient is receiving anticoagulation therapy), or PTT within normal range;

- AST and ALT ≤ 2.5 ´ upper limit of normal (ULN) or ≤ 5 ´ ULN for patients with liver
metastases; total bilirubin ≤ 1.5 ´ ULN [unless due to Gilbert's syndrome
(unconjugated hyperbilirubinemia) in which case the bilirubin should be < 3.5mg/dL);
hepatic alkaline phosphatase ≤ 2.5 ´ ULN;

- Serum creatinine ≤ 1.5 ´ ULN and calculated creatinine clearance ≥ 30 mL/min;

- Women with central nervous system (CNS) metastases are eligible if they are
clinically stable for at least 3 months after the discontinuation of prior
corticosteroid therapy;

- Female patients must be of non child-bearing potential or using effective
contraception, eg, use of oral contraceptives with an additional barrier method
(since the study drug may impair the effectiveness of oral contraceptives), double
barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam),
Depo-Provera, partner vasectomy, total abstinence, and willing to continue the
effective contraception method for 30 days after the last dose of IPI-504; and

- Patients must be able to adhere to the study visit schedule and all protocol
requirements.

Exclusion Criteria:

- Previous treatment with 17-AAG, 17-DMAG, or other known Hsp90 inhibitor;

- Concurrent radiation or surgery therapy;

- Treatment for breast cancer with any approved or investigational product, including
any local or systemic therapy within 4 weeks prior to first dose of IPI-504 in this
study;

- Initiation or discontinuation of concurrent medication that alters CYP3A activity
within 2 weeks prior to treatment with IPI-504. Patients who are on a stable dose of
drugs known to alter CYP3A activity for > 2 weeks are eligible to enroll;

- Presence of active infection or systemic use of antimicrobials within 72 hours prior
to treatment with IPI-504;

- Untreated brain metastases (patients with a history of brain metastases are eligible
as long as definitive treatment has been given and patients are clinically stable for
at least 3 months after the discontinuation of prior corticosteroid therapy);

- Significant co-morbid condition or disease which in the judgment of the Investigator
would place the patient at undue risk or interfere with the study (eg, cardiac
disease such as acute coronary syndrome or unstable angina within 6 months,
uncontrolled hypertension, arrhythmia requiring medication or mechanical control,
conduction system abnormality such as left bundle branch block or second degree heart
block, cirrhotic liver disease, cerebrovascular accident, or other conditions);

- Women who are pregnant or lactating;

- Sinus bradycardia (resting heart rate < 50 bpm) secondary to intrinsic conduction
system disease; Patients with sinus bradycardia secondary to pharmacologic treatment
may enroll if withdrawal of the treatment results in normalization of the resting
heart rate to within normal limits;

- Screening QTc > 470 msec, or previous history of QTc prolongation while taking other
medications; or

- Active or recent history (within 3 months) of keratitis or keratoconjunctivitis.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

To evaluate the antitumor activity, assessed by ORR which will be determined using RECIST, following treatment with IPI-504 in patients with locally advanced or metastatic HER2+ breast cancer that has progressed despite prior HER2-targeted therapy.

Outcome Time Frame:

30 days after discontinuation of IPI-504

Safety Issue:

No

Principal Investigator

David E. Weng, M.D., PhD

Investigator Role:

Study Director

Investigator Affiliation:

MedImmune LLC

Authority:

United States: Food and Drug Administration

Study ID:

MI-CP153

NCT ID:

NCT00627627

Start Date:

April 2008

Completion Date:

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms

Name

Location

University Hospitals Case Medical CenterCleveland, Ohio  44106
Georgetown Univ Medical Cntr, Lombardi Comprehensive Cancer Center,Washington, District of Columbia  20007
Lynn Regional Cancer - West CampusBoca Raton, Florida  33428
Medical Specialists of the Palm BeachesLake Worth, Florida  33454
"Duke University Med Cntr Breast Oncology Research ProgramDurham, North Carolina  27710
Cleveland Clinic Medical CenterCleveland, Ohio  44195
Low County Hen/OncMt. Pleasant, South Carolina  29464