Clinical trial NCT01271920: Combination of AUY922 With Trastuzumab in HER2+ Advanced Breast Cancer Patients Previously Treated With Trastuzumab
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced HER2-positive Breast Cancer
Keywords: Trastuzumab-refractory
advanced HER2-positive breast cancer,
Hsp90,
2nd or 3rd line treatment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-01-07
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 (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unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab (phase lb)
timeFrame: 4 weeks
measure: Overall Response Rate as assessed by RECIST (phase ll)
timeFrame: Every 8 weeks for the first 24 weeks and every 12 weeks thereafter
Secondary outcomes:
measure: Assess concentration of AUY922 and BJP762 in the blood at different time points (phase lb & ll)
timeFrame: 4 weeks
measure: Assess frequency, intensity and duration of Adverse Events as a Measure of Safety and Tolerability (phase lb & ll)
timeFrame: average 6 months
measure: Progression Free Survival (PFS) at the RPTD dose (phase ll only)
timeFrame: every 3 months until 24 months after the last patient has been enrolled
measure: Overall Survival (OS) at the RPTD dose
timeFrame: every 3 months until 24 months after the last patient has been enrolled
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group Dept of Highlands Oncology Grp
state: Arkansas
city: Dijon Cedex
country: France
facility: Novartis Investigative Site
city: Saint-Herblain Cédex
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Prato
country: Italy
facility: Novartis Investigative Site
state: PO
city: Candiolo
country: Italy
facility: Novartis Investigative Site
state: TO
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis Investigative Site
name: Novartis Investigative Site
role: STUDY_DIRECTOR
References:
citation: 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.