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

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unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.

Study Overview

• Status: Completed
• Conditions: Advanced HER2-positive Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab; Drug: AUY922

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Dijon Cedex, France, 21034
    • Novartis Investigative Site
  • Saint-Herblain Cédex, France, 44805
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
• Italy
  • PO
    • Prato, PO, Italy, 59100
      • Novartis Investigative Site
  • TO
    • Candiolo, TO, Italy, 10060
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28009
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
• Sweden
  • Stockholm, Sweden, SE-171 76
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TT
    • Novartis Investigative Site
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 2BX
    • Novartis Investigative Site
  • Oxford, United Kingdom, OX2 6HE
    • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group Dept of Highlands Oncology Grp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AUY922 + Trastuzumab	Drug: Trastuzumab; Drug: AUY922

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Investigative Site, Novartis Investigative Site

Publications and helpful links

General 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.

Helpful Links

• Results for CAUY922A2109 can be found on the Novartis Clinical Trials Results Website

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: November 3, 2010
• First Submitted That Met QC Criteria: January 5, 2011
• First Posted (Estimate): January 7, 2011

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Trastuzumab-refractory; advanced HER2-positive breast cancer,; Hsp90,; 2nd or 3rd line treatment
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: CAUY922A2109; 2009-015628-27 (EudraCT Number)