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

This study has been terminated.
(Limited efficacy response observed during interim analysis.)
Sponsor:
Information provided by (Responsible Party):
Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00817362
First received: January 5, 2009
Last updated: December 7, 2012
Last verified: December 2012

January 5, 2009
December 7, 2012
March 2009
August 2010   (final data collection date for primary outcome 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 [ 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 ]
Same as current
Complete list of historical versions of study NCT00817362 on ClinicalTrials.gov Archive Site
Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS) [ Time Frame: One year ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Efficacy and Safety of IPI-504 With Trastuzumab Pretreated, Locally Advanced or Metastatic HER2 Positive Breast Cancer
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

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

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

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Breast Cancer
  • HER2 Positive Breast Cancer
  • Metastatic Breast Cancer
  • Cancer of the Breast
  • Drug: IPI-504
    IPI-504 IV infusion 300 mg/m2
    Other Name: IPI-504
  • 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 Name: Herceptin
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.

Interventions:
  • Drug: IPI-504
  • Drug: Trastuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
29
May 2011
August 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Spain
 
NCT00817362
IPI-504-07
No
Infinity Pharmaceuticals, Inc.
Infinity Pharmaceuticals, Inc.
Not Provided
Study Director: Pedro Santabarbara, MD Infinity Pharmaceuticals, Inc.
Infinity Pharmaceuticals, Inc.
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP