Efficacy and Safety Evaluating IPI-504 With Trastuzumab in Patients With Pretreated, Locally Advanced or Metastatic HER2 Positive Breast Cancer - Full Text View

Sponsor:	Infinity Pharmaceuticals
Collaborator:	ICON Clinical Research
Information provided by:	Infinity Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00817362

Purpose

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

Condition	Intervention	Phase
Breast Cancer Advanced Breast Cancer Metastatic Breast Cancer Cancer of the Breast	Drug: IPI-504 and Trastuzumab	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: 17-(Allylamino)-17-demethoxygeldanamycin Trastuzumab IPI-504

U.S. FDA Resources

Further study details as provided by Infinity Pharmaceuticals:

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 [ 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 ]

Secondary Outcome Measures:

Evaluate the progression-free survival (PFS) time to progression (TTP) and overall survival(OS) [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment:	92
Study Start Date:	March 2009
Estimated Study Completion Date:	December 2011
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
IPI-504 and Trastuzumab: Experimental	Drug: 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.

Arms

Assigned Interventions

IPI-504 and Trastuzumab: Experimental

Drug: 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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 since recent systemic therapy
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00817362

Locations

United States, California
Comprehensive Cancer Center at Desert Regional Medical Center	Recruiting
1180 N. Indian Canyon Drive, Suite E-320, Palm Springs, California, United States, 92262
Contact: Claudia Fortiche 760-416-4736 CFortiche@aptiumoncology.com
Principal Investigator: Gail Leichman, M.D.
United States, Florida
Lynn Cancer Institute, Boca Raton Community Hospital 800 Meadow Road	Recruiting
Boca Raton, Florida, United States, 33431
Contact: Lori Kornish, NP 561-883-7482 lkronish@lrccw.com
Principal Investigator: Reshma Mahtani, DO
Florida Cancer Research Institute	Recruiting
Davie, Florida, United States, 33328
Contact: Debbie Seng 954-262-7606 crc@flcancercare.com
Principal Investigator: Elizabeth Tan-Chiu, MD
United States, Georgia
Peachtree Hematology-Oncology Consultants, P.C.	Recruiting
1800 Howell Mill Road, Suite 800 Atlanta, Georgia, United States, 30318
Contact: Polly Searcy 678-298-3235
Principal Investigator: Charles Henderson, M.D.
United States, Massachusetts
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Nancy Lin, MD 617-632-3800 nancy_lin@dfci.harvard.edu
Principal Investigator: Nancy Lin, MD
United States, New York
Weill Cornell Breast Center	Recruiting
425 E. 61st Street, 8th Floor, New York, New York, United States, 10065
Contact: Marta Cobham, R.N. 212-821-0780 mac2034@med.cornell.edu
Principal Investigator: Ellen Chuang, M.D.
St. Vincents Comprehensive Cancer Center	Recruiting
325 West 15th Street, New York, New York, United States, 10011
Contact: Rebekah Dunn 212-367-0181 rdunn@aptiumoncology.com
Principal Investigator: Paula Klein, M.D.
Memorial Sloan-Kettering Cancer Center	Recruiting
300 East 66th Street, New York, New York, United States, 10065
Contact: Shanu Modi, MD 646-888-4564 modis@mskcc.org
Principal Investigator: Shanu Modi, MD
United States, Tennessee
West Cancer Clinic	Recruiting
100 N. Humphreys Blvd., Suite 100, Memphis, Tennessee, United States, 38120
Contact: Tracy Stewart 901-683-0055 ext 1236 tstewart@westclinic.com
Principal Investigator: Lee Schwartzberg, M.D.
United States, Texas
US Oncology	Recruiting
Dallas, Texas, United States
Contact: Karla Burgos 281-863-4687 karla.burgos@usoncology.com
Principal Investigator: Thomas Anderson, MD
Principal Investigator: Beth Hellerstedt, MD
Principal Investigator: Frankie Ann Holmes, MD
Principal Investigator: Leonard Klein, MD
Principal Investigator: Kristi McIntyre, MD
Principal Investigator: Joyce O'Shaughnessy, MD
Principal Investigator: Devchand Paul, MD
Principal Investigator: Donald Richards, MD
Principal Investigator: Michael Savin, MD
Principal Investigator: John Smith, II, MD
Spain
Vall d'Hebron Institute of Oncology (V.H.I.O.)	Recruiting
Barcelona, Spain
Contact: Violeta Esteban Telleda +34 93 274 60 00 ext 4691 vesteban@vhebron.net
Principal Investigator: Josep Baselga

Sponsors and Collaborators

Infinity Pharmaceuticals

ICON Clinical Research

Investigators

Study Director:

Eduardo Rodenas, MD

Infinity Pharmaceuticals, Inc

More Information

No publications provided

Responsible Party:	Infinity Pharmaceticals, Inc ( Eduardo Rodenas, MD )
Study ID Numbers:	IPI-504-07
Study First Received:	January 5, 2009
Last Updated:	November 23, 2009
ClinicalTrials.gov Identifier:	NCT00817362 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Infinity Pharmaceuticals:

Breast Cancer
Advanced Breast Cancer
Metastatic Breast Cancer
HER2 Positive Breast Cancer

Cancer of the breast
Trastuzumab
Herceptin

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Therapeutic Uses

Trastuzumab
Breast Neoplasms
Pharmacologic Actions
Breast Diseases

ClinicalTrials.gov processed this record on November 30, 2009