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

Sponsor:	Infinity Pharmaceuticals, Inc.
Information provided by (Responsible Party):	Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00817362

Purpose

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

Condition	Intervention	Phase
Breast Cancer Advanced Breast Cancer Metastatic Breast Cancer Cancer of the Breast	Drug: IPI-504 and Trastuzumab	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of IPI-504 in Combination With Trastuzumab in Patients With Pretreated, Locally Advanced or Metastatic Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Trastuzumab

U.S. FDA Resources

Further study details as provided by Infinity Pharmaceuticals, Inc.:

Primary Outcome Measures:

The primary objective of the study is to evaluate overall response rate, safety, and tolerability of IPI-504 plus trastuzumab in patients with pretreated, locally advanced or metastatic HER2 positive breast cancer [ Time Frame: After initial 20 patients are enrolled and treated for one cycle - if less that 33% of the subjects experience a dose limiting toxicity an additional 26 subjects will be enrolled ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS) [ Time Frame: One year ] [ Designated as safety issue: No ]

Enrollment:	29
Study Start Date:	March 2009
Study Completion Date:	May 2011
Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: IPI-504 and Trastuzumab	Drug: 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. Other Names: IPI-504 Herceptin

Arms

Assigned Interventions

Experimental: IPI-504 and Trastuzumab

Drug: 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.

Other Names:

IPI-504
Herceptin

Detailed Description:

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00817362

Locations

United States, California
Comprehensive Cancer Center at Desert Regional Medical Center
Palm Springs, California, United States, 92262
United States, Florida
Boca Raton Comphrensive Cancer Care
Boca Raton, Florida, United States, 33431
Florida Cancer Research Institute
Davie, Florida, United States, 33328
United States, Georgia
Peachtree Hematology-Oncology Consultants, P.C.
Atlanta, Georgia, United States, 30318
Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Weill Cornell Breast Center
New York, New York, United States, 10065
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
West Cancer Clinic
Memphis, Tennessee, United States, 38120
United States, Texas
US Oncology
Dallas, Texas, United States, 76022
Spain
Vall d'Hebron Institute of Oncology (V.H.I.O.)
Barcelona, Spain

Sponsors and Collaborators

Infinity Pharmaceuticals, Inc.

Investigators

Study Director:

Robert Ross, MD

Infinity Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party:	Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00817362 History of Changes
Other Study ID Numbers:	IPI-504-07
Study First Received:	January 5, 2009
Last Updated:	May 3, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Infinity Pharmaceuticals, Inc.:

Breast Cancer
Advanced Breast Cancer
Metastatic Breast Cancer
HER2 Positive Breast Cancer

Cancer of the breast
Trastuzumab
Herceptin

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2012