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

NCT00817362 | Terminated Phase 2

• 1 other identifier: IPI-504-07
• Study Type: interventional
• Target: 29
• Locations: 2 countries
• Sites: 11

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  One year

Study Arms (1)

IPI-504 and Trastuzumab

EXPERIMENTAL

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; Drug: Trastuzumab

Interventions

IPI-504 DRUG

IPI-504 IV infusion 300 mg/m2

IPI-504 and Trastuzumab

Trastuzumab DRUG

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.

Also known as: Herceptin

IPI-504 and Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Infinity Pharmaceuticals, Inc.: lead

Study Sites (11)

Comprehensive Cancer Center at Desert Regional Medical Center

Palm Springs, California, 92262, United States

Location

Boca Raton Comphrensive Cancer Care

Boca Raton, Florida, 33431, United States

Location

Florida Cancer Research Institute

Davie, Florida, 33328, United States

Location

Peachtree Hematology-Oncology Consultants, P.C.

Atlanta, Georgia, 30318, United States

Location

Medical College of Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Breast Center

New York, New York, 10065, United States

Location

West Cancer Clinic

Memphis, Tennessee, 38120, United States

Location

US Oncology

Dallas, Texas, 76022, United States

Location

Vall d'Hebron Institute of Oncology (V.H.I.O.)

Barcelona, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tanespimycin; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pedro Santabarbara, MD

  Infinity Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2009
• First Posted: January 6, 2009
• Study Start: March 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: May 1, 2011
• Last Updated: December 11, 2012

Record last verified: 2012-12

Locations

US (10); ES (1)