A Study to Evaluate the Antitumor Activity and Safety of IPI-504 in Patients With Advanced Breast Cancer

This study has been withdrawn prior to enrollment.
(Redirect focus of the indication)
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00627627
First received: February 21, 2008
Last updated: February 1, 2010
Last verified: February 2010
  Purpose

To evaluate the antitumor activity following treatment with IPI-504 in patients with breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: IPI-504
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • 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. [ Time Frame: 30 days after discontinuation of IPI-504 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate other antitumor activities, safety, and PK parameters of IPI-504 in this patient population. [ Time Frame: 30 days after discontinuation of IPI-504 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 56
Study Start Date: April 2008
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
IPI-504
Drug: IPI-504
dose of 400 mg/m2 as a 30-60 minute IV infusion as part of a 21-day treatment cycle

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00627627

Locations
United States, District of Columbia
Georgetown Univ Medical Cntr, Lombardi Comprehensive Cancer Center,
Washington, District of Columbia, United States, 20007
United States, Florida
Lynn Regional Cancer - West Campus
Boca Raton, Florida, United States, 33428
Medical Specialists of the Palm Beaches
Lake Worth, Florida, United States, 33454
United States, North Carolina
"Duke University Med Cntr Breast Oncology Research Program
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Medical Center
Cleveland, Ohio, United States, 44195
University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44122
United States, South Carolina
Low County Hen/Onc
Mt. Pleasant, South Carolina, United States, 29464
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: David E. Weng, M.D., PhD MedImmune LLC
  More Information

No publications provided

Responsible Party: David E. Weng, M.D., Ph. D., MedImmune Inc.
ClinicalTrials.gov Identifier: NCT00627627     History of Changes
Other Study ID Numbers: MI-CP153
Study First Received: February 21, 2008
Last Updated: February 1, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 22, 2014