Efficacy and Safety of IPI-504 With Trastuzumab Pretreated, Locally Advanced or Metastatic HER2 Positive Breast Cancer

NCT ID: NCT00817362

Last Updated: 2012-12-11

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

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2011-05-31

Brief Summary

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The purpose of this study is to see if IPI-504 in combination with trastuzamab is an effective treatment in HER2 positive metastatic breast cancer

Detailed Description

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Recent clinical data has demonstrated that even in heavily pretreated patients with trastuzumab-refractory HER-2 positive breast cancer, targeting HER2 is efficacious.

IPI-504 is an HSP90 inhibitor and is chemically related to 17-AAG and it has been studied in a clinical trial in combination with trastuzamab and a response rate of 26% (7/27) was demonstrated in patients with pretreated, HER2-positive breast cancer. These data provide a strong scientific rationale for clinical testing of IPI-504 plus trastuzumab in patients with pretreated, locally advanced or metastatic HER2-positive breast cancer

Conditions

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Breast Cancer HER2 Positive Breast Cancer Metastatic Breast Cancer Cancer of the Breast

Keywords

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Breast Cancer Advanced Breast Cancer Metastatic Breast Cancer HER2 Positive Breast Cancer Cancer of the breast Trastuzumab Herceptin

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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IPI-504 and Trastuzumab

IPI-504 IV infusion 300 mg/m2 once weekly in combination with trastuzumab infusion every 3 weeks. (Continuous schedule)

Three week cycle with IPI-504 twice per week for 2 weeks and trastuzumab once per cycle followed by one week without treatment.

Trastuzumab IV infusion 8 mg/kg as the first dose of trastuzumab, followed by trastuzumab 6 mg/kg every 3 weeks. Subjects whose last dose of trastuzumab was \<4 weeks prior to study entry will receive 6 mg/kg as the first dose of trastuzumab. For all additional cycles in Stage 1, trastuzumab will be administered with the first dose of IPI-504.

IPI-504 and trastuzumab will be administered for all cycles. Until progression or unacceptable toxicity develops.

Group Type EXPERIMENTAL

IPI-504

Intervention Type DRUG

IPI-504 IV infusion 300 mg/m2

Trastuzumab

Intervention Type DRUG

Trastuzumab IV infusion 8 mg/kg as the first dose of trastuzumab, followed by trastuzumab 6 mg/kg every 3 weeks. Subjects whose last dose of trastuzumab was \<4 weeks prior to study entry will receive 6 mg/kg as the first dose of trastuzumab. For all additional cycles in Stage 1, trastuzumab will be administered with the first dose of IPI-504.

Interventions

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IPI-504

IPI-504 IV infusion 300 mg/m2

Intervention Type DRUG

Trastuzumab

Trastuzumab IV infusion 8 mg/kg as the first dose of trastuzumab, followed by trastuzumab 6 mg/kg every 3 weeks. Subjects whose last dose of trastuzumab was \<4 weeks prior to study entry will receive 6 mg/kg as the first dose of trastuzumab. For all additional cycles in Stage 1, trastuzumab will be administered with the first dose of IPI-504.

Intervention Type DRUG

Other Intervention Names

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Herceptin

Eligibility Criteria

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Inclusion Criteria

* Locally advanced/metastatic breast cancer.
* HER2-expressing primary or metastatic tumor
* Two prior regimens with HER2. Trastuzumab must have been given. No limit to prior therapies
* Measurable disease with RECIST 1.1
* Clinical progression
* LVEF WNL
* ECOG 0 or 1
* Last dose of chemotherapy, radiotherapy, surgery, ablative therapy, tyrosine kinase inhibitor, ≥2 weeks
* Administration of biological therapy ≥4 weeks
* Last dose of trastuzumab must be ≥1, or ≥3 weeks prior to start, if previously administered on an every 3 week schedule.
* Resolution of toxic effects to baseline or Grade 1, except alopecia (NCI CTCAE Version 3.0
* Organ and marrow function:

* Hemoglobin ≥8.0 g/dL
* ANC ≥1200/µL
* Platelets ≥75,000 /µL
* ALT and AST ≤ 1.5 x ULN
* Alkaline phosphatase ≤2.5 x ULN, or ≤3.0 x ULN if secondary to liver metastases.
* Serum bilirubin WNL
* Serum albumin ≥3.0 g/dL
* PT, PTT ≤1.5 x ULN
* Serum creatinine ≤1.5 x ULN
* Negative pregnancy test

Exclusion Criteria

* Prior treatment with Hsp90 inhibitor.
* Grade 4 AE secondary to trastuzumab. Grade 3/4 infusion reactions or Grade 3/4 symptomatic heart failure
* Medication/food that is a CYP3A inhibitor or inducer.
* Hx 6 months: cardiac disease - acute coronary syndrome or unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, cirrhotic liver disease, cerebrovascular accident or significant co-morbid condition
* Grade 3 or 4 hemorrhagic event within 6 months.
* HIV positivity
* Baseline QT corrected, QTcF \>470 ms
* Sinus bradycardia \<50 bpm Secondary to pharmacologic therapy may enroll if stopping therapy normalizes heart rate.
* Malignancies within 3 years other than non-melanomatous skin cancers, non-muscle-invasive bladder cancer and carcinoma in situ of cervix.
* Active keratitis or keratoconjunctivitis
* Active brain metastasis (e.g., requiring therapy with steroids or radiation therapy; or with intracranial progression 4 weeks after the completion of radiation therapy) uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous meningitis. If clinically stable brain metastasis (previously treated or untreated)are present pt is eligible.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Infinity Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pedro Santabarbara, MD

Role: STUDY_DIRECTOR

Infinity Pharmaceuticals, Inc.

Locations

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Comprehensive Cancer Center at Desert Regional Medical Center

Palm Springs, California, United States

Site Status

Boca Raton Comphrensive Cancer Care

Boca Raton, Florida, United States

Site Status

Florida Cancer Research Institute

Davie, Florida, United States

Site Status

Peachtree Hematology-Oncology Consultants, P.C.

Atlanta, Georgia, United States

Site Status

Medical College of Georgia Cancer Center

Augusta, Georgia, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Weill Cornell Breast Center

New York, New York, United States

Site Status

West Cancer Clinic

Memphis, Tennessee, United States

Site Status

US Oncology

Dallas, Texas, United States

Site Status

Vall d'Hebron Institute of Oncology (V.H.I.O.)

Barcelona, , Spain

Site Status

Countries

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United States Spain

Other Identifiers

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IPI-504-07

Identifier Type: -

Identifier Source: org_study_id