Advanced HER2-positive Breast CancerPhase 1/2NCT01271920
Combination of AUY922 With Trastuzumab in HER2+ Advanced Breast Cancer Patients Previously Treated With Trastuzumab
A Phase 1/2 study testing AUY922 and Trastuzumab in people with Advanced HER2-positive Breast Cancer, run by Novartis Pharmaceuticals at 16 sites in 8 countries.
Trial summary
The phase Ib part of the trial will assess the MTD of AUY922 in combination with Trastuzumab in patients with Trastuzumab-refractory locally advanced or metastatic HER2+. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment (28 days) medically unacceptable dose limiting toxicity… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced HER2-positive Breast Cancer
- What is being tested?
- AUY922 and Trastuzumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 16 sitesin 8 countries
- Study dates
- Sep 2010to Oct 2013
- 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
- Female patients with confirmed HER-2 positive , non-operable locally advanced or metastatic breast cancer
- All patients must have received at least 1 but no more than 2 prior anti HER2 based regimens including at least 1 regimen containing Trastuzumab.
- All patients must have at least one measurable lesion as defined by RECIST criteria.
- All patients must have documented progressive disease following the last line of therapy before entering the study
- ECOG Performance status ≤ 1
Who cannot join
- Patients with known CNS metastasis which are: symptomatic or require treatment for symptom control and/or growing
- Prior treatment with any HSP90 or HDAC inhibitor
- Impaired cardiac function
- Acute or chronic liver or renal disease
- Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY922
- Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
- Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
16 sites in 8 countries.
16 sites in 8 countries
United Kingdom4 sites
Novartis Investigative Site
Birmingham, B15 2TT
Novartis Investigative Site
Leicester, LE1 5WW
Novartis Investigative Site
Manchester, M20 2BX
Novartis Investigative Site
Oxford, OX2 6HE
Spain3 sites
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Málaga, Andalusia, 29010
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706
France2 sites
Novartis Investigative Site
Dijon, 21034
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Germany2 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Tübingen, 72076
Italy2 sites
Novartis Investigative Site
Candiolo, TO, 10060
Novartis Investigative Site
Prato, PO, 59100
United States1 site
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, 72703
About this study
Official title: A Phase Ib/II, Multi-center, Open-label Study to Evaluate the Efficacy of AUY922 in Combination With Trastuzumab in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer, That Has Progressed After or During at Least One Trastuzumab-containing Regimen
The phase Ib part of the trial will assess the MTD of AUY922 in combination with Trastuzumab in patients with Trastuzumab-refractory locally advanced or metastatic HER2+. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment (28 days) medically unacceptable dose limiting toxicity (DLT).
The phase II part of the trial will assess any potential effect on efficacy of adding AUY922 to Trastuzumab in patients with Trastuzumab-refractory locally advanced or metastatic HER2+ breast cancer.
Both AUY922 and Trastuzumab will be administered as a weekly IV infusion. Treatment should be continued as long as the patient does not have disease progression and tolerates the treatment. The following reasons are examples of acceptable reasons for discontinuing the study; tumor progression (by RECIST, as assessed by the investigator), unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.
- Conditions
- Advanced HER2-positive Breast Cancer
- Being tested
- AUY922, Trastuzumab
- Keywords
- Trastuzumab-refractory, advanced HER2-positive breast cancer,, Hsp90,, 2nd or 3rd line treatment
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AUY922Drug
TrastuzumabDrug
| Study group | Role | What they receive |
|---|---|---|
| AUY922 + Trastuzumab | Experimental | Not described Receives: Drug: AUY922; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab (phase lb)
Measured: 4 weeks
Overall Response Rate as assessed by RECIST (phase ll)
Measured: Every 8 weeks for the first 24 weeks and every 12 weeks thereafter
Secondary outcomes (4)
Assess concentration of AUY922 and BJP762 in the blood at different time points (phase lb & ll)
Measured: 4 weeks
Assess frequency, intensity and duration of Adverse Events as a Measure of Safety and Tolerability (phase lb & ll)
Measured: average 6 months
Progression Free Survival (PFS) at the RPTD dose (phase ll only)
Measured: every 3 months until 24 months after the last patient has been enrolled
Overall Survival (OS) at the RPTD dose
Measured: every 3 months until 24 months after the last patient has been enrolled
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2011 (estimated)
- Study startSep 2010
- Primary completionOct 2013
- Study completionOct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced HER2-positive 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis PharmaceuticalsNovartis Investigative Site, Study director, Novartis Investigative Site
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01271920
- Sponsor's protocol ID
- CAUY922A2109
- Other IDs
- 2009-015628-27, 2009
- Status last verified
- Feb 2017
- First submitted
- 3 Nov 2010
- Last updated
- 8 Dec 2020
- Results posted
- No
Publications
Kong A, Rea D, Ahmed S, Beck JT, Lopez Lopez R, Biganzoli L, Armstrong AC, Aglietta M, Alba E, Campone M, Hsu Schmitz SF, Lefebvre C, Akimov M, Lee SC. Phase 1B/2 study of the HSP90 inhibitor AUY922 plus trastuzumab in metastatic HER2-positive breast cancer patients who have progressed on trastuzumab-based regimen. Oncotarget. 2016 Jun 21;7(25):37680-37692. doi: 10.18632/oncotarget.8974.
PubMed 27129177
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II, Multi-center, Open-label Study to Evaluate the Efficacy of AUY922 in Combination With Trastuzumab in Patients With Locally Advanced or Metastatic HER2-positive Breast Cancer, That Has Progressed After or During at Least One Trastuzumab-containing Regimen
- ClinicalTrials.gov ID
- NCT01271920
- Acronym / sponsor ID
- CAUY922A2109
- Conditions
- Advanced HER2-positive Breast Cancer
- Keywords
- Trastuzumab-refractory, advanced HER2-positive breast cancer,, Hsp90,, 2nd or 3rd line treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Sep 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 7 Jan 2011 (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.
The phase Ib part of the trial will assess the MTD of AUY922 in combination with Trastuzumab in patients with Trastuzumab-refractory locally advanced or metastatic HER2+. The MTD is defined as the highest drug dosage not causing in the first cycle of treatment (28 days) medically unacceptable dose limiting toxicity (DLT).
The phase II part of the trial will assess any potential effect on efficacy of adding AUY922 to Trastuzumab in patients with Trastuzumab-refractory locally advanced or metastatic HER2+ breast cancer.
Both AUY922 and Trastuzumab will be administered as a weekly IV infusion. Treatment should be continued as long as the patient does not have disease progression and tolerates the treatment. The following reasons are examples of acceptable reasons for discontinuing the study; tumor progression (by RECIST, as assessed by the investigator), unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AUY922 + Trastuzumab | Experimental | Drug: AUY922, Drug: Trastuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Female patients with confirmed HER-2 positive , non-operable locally advanced or metastatic breast cancer
- All patients must have received at least 1 but no more than 2 prior anti HER2 based regimens including at least 1 regimen containing Trastuzumab.
- All patients must have at least one measurable lesion as defined by RECIST criteria.
- All patients must have documented progressive disease following the last line of therapy before entering the study
- ECOG Performance status ≤ 1
Key exclusion criteria (8 listed)
- Patients with known CNS metastasis which are: symptomatic or require treatment for symptom control and/or growing
- Prior treatment with any HSP90 or HDAC inhibitor
- Impaired cardiac function
- Acute or chronic liver or renal disease
- Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTc interval or inducing Torsades de Pointes and cannot be switched or discontinued to an alternative drug prior to commencing AUY922
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 | Drug | AUY922 + Trastuzumab |
| Trastuzumab | Drug | AUY922 + Trastuzumab |
Primary outcome
Maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab (phase lb)
Time frame: 4 weeks
Overall Response Rate as assessed by RECIST (phase ll)
Time frame: Every 8 weeks for the first 24 weeks and every 12 weeks thereafter
4 secondary outcomes
Assess concentration of AUY922 and BJP762 in the blood at different time points (phase lb & ll)
Time frame: 4 weeks
Assess frequency, intensity and duration of Adverse Events as a Measure of Safety and Tolerability (phase lb & ll)
Time frame: average 6 months
Progression Free Survival (PFS) at the RPTD dose (phase ll only)
Time frame: every 3 months until 24 months after the last patient has been enrolled
Overall Survival (OS) at the RPTD dose
Time frame: every 3 months until 24 months after the last patient has been enrolled
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 8 Dec 2020.
- Results publication: PubMed 27129177Kong A, Rea D, Ahmed S, Beck JT, Lopez Lopez R, Biganzoli L, Armstrong AC, Aglietta M, Alba E, Campone M, Hsu Schmitz SF, Lefebvre C, Akimov M, Lee SC. Phase 1B/2 study of the HSP90 inhibitor AUY922 plus trastuzumab in metastatic HER2-positive breast cancer patients who have progressed on trastuzumab-based regimen. Oncotarget. 2016 Jun 21;7(25):37680-37692. doi: 10.18632/oncotarget.8974.
- Results for CAUY922A2109 can be found on the Novartis Clinical Trials Results 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
Novartis Investigative Site study director
Novartis Investigative Site
16 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AUY922 and Trastuzumab in people with Advanced HER2-positive Breast Cancer, run by Novartis Pharmaceuticals at 16 sites in 8 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 5 inclusion and 8 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 8 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 16 sites in United Kingdom, Spain, France, Germany, Italy and 3 more countries. 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?
Maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab (phase lb) (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01271920, which also lists 1 linked publication.
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 8 Dec 2020.