Clinical trial NCT00817362: Efficacy and Safety of IPI-504 With Trastuzumab Pretreated, Locally Advanced or Metastatic HER2 Positive Breast Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
HER2 Positive Breast Cancer
Metastatic Breast Cancer
Cancer of the Breast
Keywords: Breast Cancer
Advanced Breast Cancer
Metastatic Breast Cancer
HER2 Positive Breast Cancer
Cancer of the breast
Trastuzumab
Herceptin
Lead sponsor: Infinity Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2009-01-06
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: 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 outcomes:
measure: Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS)
timeFrame: One year
Other outcomes:
Locations:
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center at Desert Regional Medical Center
state: California
city: Boca Raton
country: United States
facility: Boca Raton Comphrensive Cancer Care
state: Florida
city: Davie
country: United States
facility: Florida Cancer Research Institute
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology-Oncology Consultants, P.C.
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia Cancer Center
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Breast Center
state: New York
city: Memphis
country: United States
facility: West Cancer Clinic
state: Tennessee
city: Dallas
country: United States
facility: US Oncology
state: Texas
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology (V.H.I.O.)
Study officials:
affiliation: Infinity Pharmaceuticals, Inc.
name: Pedro Santabarbara, MD
role: STUDY_DIRECTOR
References: