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

Primary Purpose

Breast Cancer, HER2 Positive Breast Cancer, Metastatic Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IPI-504
Trastuzumab
Sponsored by
Infinity Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer, HER2 Positive Breast Cancer, Cancer of the breast, Trastuzumab, Herceptin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Comprehensive Cancer Center at Desert Regional Medical Center
  • Boca Raton Comphrensive Cancer Care
  • Florida Cancer Research Institute
  • Peachtree Hematology-Oncology Consultants, P.C.
  • Medical College of Georgia Cancer Center
  • Dana-Farber Cancer Institute
  • Memorial Sloan-Kettering Cancer Center
  • Weill Cornell Breast Center
  • West Cancer Clinic
  • US Oncology
  • Vall d'Hebron Institute of Oncology (V.H.I.O.)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IPI-504 and Trastuzumab

Arm Description

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.

Outcomes

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

Secondary Outcome Measures

Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS)

Full Information

First Posted
January 5, 2009
Last Updated
December 7, 2012
Sponsor
Infinity Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00817362
Brief Title
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

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Terminated
Why Stopped
Limited efficacy response observed during interim analysis.
Study Start Date
March 2009 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Infinity Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. 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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IPI-504 and Trastuzumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IPI-504
Intervention Description
IPI-504 IV infusion 300 mg/m2
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS)
Time Frame
One year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pedro Santabarbara, MD
Organizational Affiliation
Infinity Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Comprehensive Cancer Center at Desert Regional Medical Center
City
Palm Springs
State/Province
California
ZIP/Postal Code
92262
Country
United States
Facility Name
Boca Raton Comphrensive Cancer Care
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33431
Country
United States
Facility Name
Florida Cancer Research Institute
City
Davie
State/Province
Florida
ZIP/Postal Code
33328
Country
United States
Facility Name
Peachtree Hematology-Oncology Consultants, P.C.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Medical College of Georgia Cancer Center
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Weill Cornell Breast Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
West Cancer Clinic
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
US Oncology
City
Dallas
State/Province
Texas
ZIP/Postal Code
76022
Country
United States
Facility Name
Vall d'Hebron Institute of Oncology (V.H.I.O.)
City
Barcelona
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

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

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