Advanced HER2-positive Breast Cancer Clinical Trial
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
| Verified date | February 2017 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.
| Status | Completed |
| Enrollment | 45 |
| Est. completion date | October 2013 |
| Est. primary completion date | October 2013 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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 |
| Country | Name | City | State |
|---|---|---|---|
| France | Novartis Investigative Site | Dijon Cedex | |
| France | Novartis Investigative Site | Saint-Herblain Cédex | |
| Germany | Novartis Investigative Site | Essen | |
| Germany | Novartis Investigative Site | Tuebingen | |
| Italy | Novartis Investigative Site | Candiolo | TO |
| Italy | Novartis Investigative Site | Prato | PO |
| Singapore | Novartis Investigative Site | Singapore | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Malaga | Andalucia |
| Spain | Novartis Investigative Site | Santiago de Compostela | Galicia |
| Sweden | Novartis Investigative Site | Stockholm | |
| United Kingdom | Novartis Investigative Site | Birmingham | |
| United Kingdom | Novartis Investigative Site | Leicester | |
| United Kingdom | Novartis Investigative Site | Manchester | |
| United Kingdom | Novartis Investigative Site | Oxford | |
| United States | Highlands Oncology Group Dept of Highlands Oncology Grp | Fayetteville | Arkansas |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, France, Germany, Italy, Singapore, Spain, Sweden, United Kingdom,
Kong A, Rea D, Ahmed S, Beck JT, López López 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 canc — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab (phase lb) | 4 weeks | ||
| Primary | Overall Response Rate as assessed by RECIST (phase ll) | Every 8 weeks for the first 24 weeks and every 12 weeks thereafter | ||
| Secondary | Assess concentration of AUY922 and BJP762 in the blood at different time points (phase lb & ll) | 4 weeks | ||
| Secondary | Assess frequency, intensity and duration of Adverse Events as a Measure of Safety and Tolerability (phase lb & ll) | average 6 months | ||
| Secondary | Progression Free Survival (PFS) at the RPTD dose (phase ll only) | every 3 months until 24 months after the last patient has been enrolled | ||
| Secondary | Overall Survival (OS) at the RPTD dose | every 3 months until 24 months after the last patient has been enrolled |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01921335 -
ARRY-380 + Trastuzuamab for Breast w/ Brain Mets
|
Phase 1 |