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

Texas Tech University Health Sciences Center, El Paso

Status and phase

Withdrawn

Phase 2

Phase 1

Conditions

Breast Cancer

ER Positive Breast Cancer

Metastatic Breast Cancer

HER-2 Positive Breast Cancer

Treatments

Drug: AUY922

Study type

Interventional

Funder types

Other

Identifiers

NCT01361945

CAUY922ZN11

Details and patient eligibility

About

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 +.

Full description

The dose and schedule of AUY922 is the MTD dose identified in the phase I, given as 1 hour infusion weekly.

The Phase II component will have a 2 stage design single arm design. (Section 9.0). Overall response rate (ORR) is the primary endpoint. Estimated N=40 (12 in first stage) .A total of 39 response-evaluable participants is required. In the first stage, 12 response-evaluable participants will be accrued; if there are 3 or fewer CR+PRs, the study will stop for futility. There is a 55% probability of stopping early if, in fact, the ORR is 28%. If there are 4 or more CR+PRs, the study will proceed to the second stage and an additional 27 response-evaluable participants will be accrued. We will accrue 1 additional patient (then the needed 39 to account for attrition)

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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