Breast Cancer, Hematologic Neoplasms
Conditions
Keywords
AUY922, Solid tumors, Breast Cancer, Phase I/II, Advanced Solid malignancies (Phase I), Breast Cancer ( Phase II ), HER2+, ER+, HSP90
Brief summary
This is a phase I/II, open-label, multicenter study of AUY922 administered intravenously in patients with advanced solid malignancies to determine the maximum tolerated dose. Phase II expansion arms will investigate efficacy in patients with either HER2 positive or ER positive locally advanced or metastatic breast cancer. Additional patients with advanced solid malignancies will also be investigated in a separate expansion arm. Safety, pharmacokinetics and pharmacodynamics will be assessed.
Interventions
DRUGAUY922 2 mg/m2
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Dose-escalation and MTD dose expansion arm: Patients with histologically confirmed, advanced malignant solid tumors whose disease has progressed on standard therapy or for whom no standard therapy exists. Breast cancer phase II expansion arms only: 1. Females patients with HER2 positive non-operable locally advanced or metastatic breast cancer must have: * History of trastuzumab resistance, defined as either local or systemic disease progression on treatment with at least 8 weeks of a trastuzumab containing regimen. * Received up to 3 prior anti HER2 based regimens (i.e. trastuzumab and/or lapatinib in combination with other agents) for metastatic disease * Patients who develop metastases while receiving adjuvant or neo-adjuvant trastuzumab are eligible. HER2 positive patients, tumor/s must demonstrate HER2 over-expression based on either: * Immunohistochemistry (IHC) at the 3+ level, or * IHC 2+ confirmed by fluorescence in-situ hybridization (FISH). Tumors tested by FISH must be positive by the specific FISH assay for the amplification of HER2. 2. Female patients with ER positive non-operable locally advanced or metastatic breast cancer patients who received standard sequence lines of endocrine therapy and whose disease has progressed on at least one and up to 3 lines of endocrine and/or cytotoxic therapy for advanced disease. 2. All patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression. 3. All patients must have progressive disease before entering the study 4. Age ≥ 18 years. 5. World Health Organization (WHO) Performance Status of ≤ 2. 6. Life expectancy of ≥ 12 weeks. 7. Absolute Neutrophil Count (ANC) 1.5 x 109/L; hemoglobin (Hgb) 9 g/dl; platelets (plt) 100 x 109/L; potassium, calcium, magnesium and phosphorus within normal limits or correctable with supplements; AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present; serum bilirubin 1.5 x ULN; serum albumin \> 2.5g/dl and serum creatinine 1.5 x ULN or 24-hour clearance 50 ml/min
Exclusion criteria
1. Patients with CNS metastasis which are: * Symptomatic or * Require treatment for symptom control and/or * Growing Note: patients without clinical signs or symptoms of CNS involvement are not required to have a CT/MRI of the brain 2. Prior treatment with any HSP90 or HDAC inhibitor compound. 3. Patient who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames: * Chemotherapy within 4 weeks * Radiotherapy within 4 weeks * Palliative radiotherapy: within 2 weeks * Trastuzumab treatment within 4 weeks * Nitrosoureas, mitomycin and monoclonal antibodies (except trastuzumab): within 6 weeks * Any continuous-dosing (i.e. daily dosing, every-other-day dosing, Monday- Wednesday-Friday dosing, weekly etc) of systemic anticancer treatment for which the recovery period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤ 5 half lives of the agent and their active metabolites (if any) 4. Patients who have not recovered from side effects of previous systemic anticancer therapy to less than grade 2 CTCAE prior to the first dose. 5. Pregnant or lactating women. 6. Cardia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The safe dose of AUY922 when administered once a week | 54 weeks (MTD determination) |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy of AUY922 administered once a week | Baseline, and every 2 cycles (time to document tumor progression) |
| Pharmacokinetics of AUY922 and Pharmacodynamics by PET response, blood and tumor biomarkers at baseline and post-AUY922 | Baseline and every 2 cycles |
Countries
Netherlands, Switzerland, United Kingdom, United States
Outcome results
None listed