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

Sponsor

Infinity Pharmaceuticals, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00817362

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer HER2 Positive Breast Cancer Metastatic Breast Cancer Cancer of the Breast	Drug: IPI-504 Drug: Trastuzumab	Phase 2

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

Study Design

Study Type:

Interventional

Actual Enrollment :

29 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Mar 1, 2009

Actual Primary Completion Date :

Aug 1, 2010

Actual Study Completion Date :

May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: IPI-504 IPI-504 IV infusion 300 mg/m2 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. Other Names: Herceptin

Arm

Intervention/Treatment

Experimental: 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.

Drug: IPI-504

IPI-504 IV infusion 300 mg/m2

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.

Other Names:

Herceptin

Outcome Measures

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 [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]

Secondary Outcome Measures

Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS) [One year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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