Breast CancerPhase 1/2NCT00526045
Phase I-II Study to Determine the Maximum Tolerated Dose (MTD) of AUY922 in Advanced Solid Malignancies, and Efficacy in HER2+ or ER+ Locally Advanced or Metastatic Breast Cancer Patients
A Phase 1/2 study testing AUY922 2 mg/m2 in people with Breast Cancer and Hematologic Neoplasms, run by Novartis Pharmaceuticals at 10 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Hematologic Neoplasms
- What is being tested?
- AUY922 2 mg/m2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 10 sitesin 4 countries
- Study dates
- Jul 2007to Apr 2012
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
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- 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.
- 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.
- All patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression.
- All patients must have progressive disease before entering the study
- Age ≥ 18 years.
- World Health Organization (WHO) Performance Status of ≤ 2.
- Life expectancy of ≥ 12 weeks.
- 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
Who cannot join
- 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
- Prior treatment with any HSP90 or HDAC inhibitor compound.
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- 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)
- Patients who have not recovered from side effects of previous systemic anticancer therapy to less than grade 2 CTCAE prior to the first dose.
- Pregnant or lactating women.
- Cardia exclusion criteria:
- History (or family history) of long QT syndrome.
- Mean QTc ≥ 450 msec on screening ECG
- History of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina, coronary arteriography or cardiac stress testing/imaging with findings consistent with coronary occlusion or infarction, ≤ 6 months prior to study start.
- History of heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO
- Known diagnosis of HIV infection (HIV testing is not mandatory).
- Acute or chronic liver disease, acute or chronic renal disease or other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes, active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol.
- Cardiac exclusion criteria:
- Mean QTc ≥ 450 msec on screening ECG and clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevations or depressions > 1mm, or 2nd (Mobitz II) or 3rd degree AV block; clinically significant ECG abnormalities including one or more of the following: left bundle branch block (LBBB), right bundle branch block (RBBB) with left anterior hemiblock (LAHB). ST segment elevations or depressions > 1mm, or 2nd (Mobitz II) or 3rd degree AV block.
- History (or family history) of long QT syndrome, heart failure or left ventricular (LV) dysfunction (LVEF ≤ 45%) by MUGA or ECHO, history of clinically manifest ischemic heart disease including myocardial infarction, stable or unstable angina, coronary arteriography or cardiac stress testing/imaging with findings consistent with coronary occlusion or infarction, ≤ 6 months prior to study start; history or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
10 sites in 4 countries.
10 sites in 4 countries
United States7 sites
Georgia Health Sciences University Med College of GA
Augusta, Georgia, 30912
Dana Farber Cancer Institute StudyCoordinator:CAUY922A2101
Boston, Massachusetts, 02115
MD Anderson Cancer Center/University of Texas Thoractic Head/Neck Med.Onc(2)
Houston, Texas, 77030-4009
Nevada Cancer Institute Clinical Trials Office
Las Vegas, Nevada, 89135
UCLA/ University of California Los Angeles UCLA
Los Angeles, California, 90095
Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(3)
San Antonio, Texas, 78229
Washington University School Of Medicine-Siteman Cancer Ctr Dept. of Siteman Cancer Ctr.
St Louis, Missouri, 63110
About this study
Official title: A Phase I Dose Escalation, Multi-center, Open-label Study of AUY922 Administered IV on a Once Weekly Schedule in Adult Patients With Advanced Solid Malignancies Including Phase II Expansion Arms in Patients With Either HER2 Positive or ER Positive Locally Advanced or Metastatic Breast Cancer.
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.
- Conditions
- Breast Cancer, Hematologic Neoplasms
- Being tested
- AUY922 2 mg/m2
- Keywords
- AUY922, Solid tumors, Breast Cancer, Phase I/II, Advanced Solid malignancies (Phase I), Breast Cancer ( Phase II ), HER2+, ER+, HSP90
- Medical subject headings
- Breast Neoplasms, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AUY922 2 mg/m2Drug
| Study group | Role | What they receive |
|---|---|---|
| Escalation | Experimental | Not described Receives: Drug: AUY922 2 mg/m2 |
| HER2 Positive | Experimental | Not described Receives: Drug: AUY922 2 mg/m2 |
| ER+ breast cancer | Experimental | Not described Receives: Drug: AUY922 2 mg/m2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safe dose of AUY922 when administered once a week
Measured: 54 weeks (MTD determination)
Secondary outcomes (2)
Efficacy of AUY922 administered once a week
Measured: 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
Measured: Baseline and every 2 cycles
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2007 (estimated)
- Study startJul 2007
- Primary completionApr 2012
- Study completionApr 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 117 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00526045
- Sponsor's protocol ID
- CAUY922A2101
- Other IDs
- 2006-002766-20
- Status last verified
- May 2013
- First submitted
- 5 Sep 2007
- Last updated
- 17 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation, Multi-center, Open-label Study of AUY922 Administered IV on a Once Weekly Schedule in Adult Patients With Advanced Solid Malignancies Including Phase II Expansion Arms in Patients With Either HER2 Positive or ER Positive Locally Advanced or Metastatic Breast Cancer.
- ClinicalTrials.gov ID
- NCT00526045
- Acronym / sponsor ID
- CAUY922A2101
- Conditions
- Breast Cancer, Hematologic Neoplasms
- Keywords
- AUY922, Solid tumors, Breast Cancer, Phase I/II, Advanced Solid malignancies (Phase I), Breast Cancer ( Phase II ), HER2+, ER+
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 117 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 6 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Escalation | Experimental | Drug: AUY922 2 mg/m2 |
| HER2 Positive | Experimental | Drug: AUY922 2 mg/m2 |
| ER+ breast cancer | Experimental | Drug: AUY922 2 mg/m2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
- All patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression.
- All patients must have progressive disease before entering the study
- Age ≥ 18 years.
- World Health Organization (WHO) Performance Status of ≤ 2.
Key exclusion criteria (26 listed)
- Patients with CNS metastasis which are:
- Note: patients without clinical signs or symptoms of CNS involvement are not required to have a CT/MRI of the brain
- Prior treatment with any HSP90 or HDAC inhibitor compound.
- Patient who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames:
- Patients who have not recovered from side effects of previous systemic anticancer therapy to less than grade 2 CTCAE prior to the first dose.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AUY922 2 mg/m2 | Drug | ER+ breast cancer, Escalation, HER2 Positive |
Primary outcome
The safe dose of AUY922 when administered once a week
Time frame: 54 weeks (MTD determination)
2 secondary outcomes
Efficacy of AUY922 administered once a week
Time frame: 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
Time frame: Baseline and every 2 cycles
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Resutls for CAUY922A2101 on the Novartis clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
10 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AUY922 2 mg/m2 in people with Breast Cancer and Hematologic Neoplasms, run by Novartis Pharmaceuticals at 10 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Netherlands, Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The safe dose of AUY922 when administered once a week (time frame: 54 weeks (MTD determination)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020; AzTrials last refreshed its copy on 26 Oct 2026.