Combination of AUY922 With Trastuzumab in HER2+ Advanced Breast Cancer Patients Previously Treated With Trastuzumab

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01271920

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

2.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.

Condition or Disease	Intervention/Treatment	Phase
Advanced HER2-positive Breast Cancer	Drug: AUY922 Drug: Trastuzumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

45 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2010

Actual Primary Completion Date :

Oct 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AUY922 + Trastuzumab	Drug: AUY922 Drug: Trastuzumab

Arm

Intervention/Treatment

Experimental: AUY922 + Trastuzumab

Drug: AUY922

Drug: Trastuzumab

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab (phase lb) [4 weeks]
Overall Response Rate as assessed by RECIST (phase ll) [Every 8 weeks for the first 24 weeks and every 12 weeks thereafter]

Secondary Outcome Measures

Assess concentration of AUY922 and BJP762 in the blood at different time points (phase lb & ll) [4 weeks]
Assess frequency, intensity and duration of Adverse Events as a Measure of Safety and Tolerability (phase lb & ll) [average 6 months]
Progression Free Survival (PFS) at the RPTD dose (phase ll only) [every 3 months until 24 months after the last patient has been enrolled]
Overall Survival (OS) at the RPTD dose [every 3 months until 24 months after the last patient has been enrolled]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group Dept of Highlands Oncology Grp	Fayetteville	Arkansas	United States	72703
2	Novartis Investigative Site	Dijon Cedex		France	21034
3	Novartis Investigative Site	Saint-Herblain Cédex		France	44805
4	Novartis Investigative Site	Essen		Germany	45147
5	Novartis Investigative Site	Tuebingen		Germany	72076
6	Novartis Investigative Site	Prato	PO	Italy	59100
7	Novartis Investigative Site	Candiolo	TO	Italy	10060
8	Novartis Investigative Site	Singapore		Singapore	119228
9	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
10	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
11	Novartis Investigative Site	Madrid		Spain	28009
12	Novartis Investigative Site	Stockholm		Sweden	SE-171 76
13	Novartis Investigative Site	Birmingham		United Kingdom	B15 2TT
14	Novartis Investigative Site	Leicester		United Kingdom	LE1 5WW
15	Novartis Investigative Site	Manchester		United Kingdom	M20 2BX
16	Novartis Investigative Site	Oxford		United Kingdom	OX2 6HE