Breast Cancer, Cancer of the Breast, HER2 Positive Breast Cancer, Metastatic Breast Cancer
Conditions
Keywords
Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer, HER2 Positive Breast Cancer, Cancer of the breast, Trastuzumab, Herceptin
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
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
Interventions
DRUGIPI-504
IPI-504 IV infusion 300 mg/m2
DRUGTrastuzumab
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.
Sponsors
Infinity Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS) | One year |
Countries
Spain, United States
Outcome results
None listed