AUY922 With Lapatinib and Letrozole for ER+ HER2+ Advanced Breast Cancer

This study has been withdrawn prior to enrollment.
(Closed due to no enrollment)
Sponsor:
Information provided by (Responsible Party):
Texas Tech University Health Sciences Center
ClinicalTrials.gov Identifier:
NCT01361945
First received: May 24, 2011
Last updated: September 26, 2012
Last verified: September 2012
  Purpose

The purpose of this study is to find out what effects, administering infusions of AUY922 with hormonal therapy (letrozole) and oral targeted drug (lapatinib) will have on the patients with advanced breast cancer known as ER+ HER2 +.


Condition Intervention Phase
Breast Cancer
Metastatic Breast Cancer
HER-2 Positive Breast Cancer
ER Positive Breast Cancer
Drug: AUY922
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/ II, Multi-center, Open-label Study, to Evaluate the Efficacy of AUY922 in Combination With Lapatinib With Letrozole in Postmenopausal Patients With Locally Advanced or Metastatic ER+ , HER2 + Breast Cancer

Resource links provided by NLM:


Further study details as provided by Texas Tech University Health Sciences Center:

Primary Outcome Measures:
  • Overall Response Rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: July 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AUY922
Single Arm
Drug: AUY922
AUY 922 is given intravenously weekly; letrozole and lapatinib are given orally

  Eligibility

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

Inclusion Criteria:

  • Age 18 years
  • Able to sign Informed Consent
  • Patients must have the following laboratory values:

Absolute Neutrophil Count (ANC) 1.5x109/L Hemoglobin (Hgb) 9 g/dl Platelets (plt) 100x109/L

  • Potassium within normal limits
  • Total calcium (corrected for serum albumin) and Phosphorus within normal limits
  • Magnesium above LLN or correctable with supplements
  • AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN) if AP > 2.5 ULN
  • AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if AP ≤ 5.0 x ULN if
  • Serum bilirubin 1.5 x ULN
  • Serum creatinin 1.5 x ULN or 24-hour clearance 50 ml/min
  • Negative serum pregnancy test. The serum pregnancy test must be obtained prior to the first administration of AUY922 (≤ 72 hours prior to dosing) in all pre-menopausal women and women <2 years after the onset of menopause
  • Histologically confirmed HER2 + and ER+ or PR + (i.e., HR+) Postmenopausal women with Metastatic breast cancer or resistant locally advanced breast cancer.
  • Stage of disease (stage IIIb/c not responding or progressing to standard therapy with trastuzumab) or stage IV receiving first line treatment in the metastatic setting . All patients should have documented clinical progression prior to entering study
  • Prior chemotherapy for metastatic stage IV disease is prohibited for patients enrolled in phase II, but allowed up to 3 lines for patients enrolled in Phase I. Prior neoadjuvant/adjuvant chemotherapy, antiestrogens, and radiotherapy are allowed. Adjuvant hormonal therapy including aromatase inhibitors are permitted in the adjuvant, neoadjuvant or metastatic setting if discontinued at least two weeks prior to starting study treatment. Trastuzumab is permitted in the adjuvant, neoadjuvant or metastatic setting if discontinued at least 4 weeks prior to study treatment
  • Patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions and non-measurable disease are only evaluable for disease progression
  • Patients must have tumors that carry HER-2 gene amplifications as determined by (i) fluorescence in situ hybridization (FISH) or (ii) overexpression of HER-2 protein 3+ level assessed by immunohistochemistry. Patients who have previously been treated with trastuzumab must be off treatment at least 6 weeks prior to starting study treatment.
  • World Health Organization (WHO) Performance Status of < 1
  • Life expectancy of > 12 weeks

Exclusion Criteria:

  • Unresolved diarrhea ≥ CTCAE (v4.02) grade 1
  • Pregnant or lactating women
  • Impaired cardiac function, including any one of the following:
  • History (or family history) of long QT syndrome
  • Mean QTc ≥ 450 msec on baseline ECG
  • History of clinically manifested ischemic heart disease ≤ 6 months prior to study start or History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO or arrythmia
  • Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggesting HIV infection.
  • Known hypersensitivity to any of the study drugs or their excipients
  • Participation in another clinical study within 30 days before first study treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01361945

Sponsors and Collaborators
Texas Tech University Health Sciences Center
Investigators
Principal Investigator: Zeina Nahleh, M.D. Texas Tech University Health Sciences Center
  More Information

No publications provided

Responsible Party: Texas Tech University Health Sciences Center
ClinicalTrials.gov Identifier: NCT01361945     History of Changes
Other Study ID Numbers: CAUY922ZN11
Study First Received: May 24, 2011
Last Updated: September 26, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Texas Tech University Health Sciences Center:
ER+
HER2+
Breast

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Lapatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 23, 2014