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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00817362
• Other study ID #: IPI-504-07
• Status: Terminated
• Phase: Phase 2
• First received: January 5, 2009
• Last updated: December 7, 2012
• Start date: March 2009
• Est. completion date: May 2011

Study information

• Verified date: December 2012
• Source: Infinity Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: May 2011
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Cancer of the Breast
• HER2 Positive Breast Cancer
• Metastatic Breast Cancer

Intervention

Drug:
• IPI-504
IPI-504 IV infusion 300 mg/m2
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Infinity Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		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	Yes
Secondary	Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS)		One year	No