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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01271920
First received: November 3, 2010
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

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unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.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 Intervention Phase
Advanced HER2-positive Breast Cancer
Drug: AUY922
Drug: Trastuzumab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) and/or recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab (phase lb) [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  • Overall Response Rate as assessed by RECIST (phase ll) [ Time Frame: Every 8 weeks for the first 24 weeks and every 12 weeks thereafter ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess concentration of AUY922 and BJP762 in the blood at different time points (phase lb & ll) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
  • Assess frequency, intensity and duration of Adverse Events as a Measure of Safety and Tolerability (phase lb & ll) [ Time Frame: average 6 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall Survival (OS) at the RPTD dose [ Time Frame: every 3 months until 24 months after the last patient has been enrolled ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: September 2010
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AUY922 + Trastuzumab Drug: AUY922 Drug: Trastuzumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01271920

Locations
United States, Arkansas
Highlands Oncology Group Dept of Highlands Oncology Grp
Fayetteville, Arkansas, United States, 72703
France
Novartis Investigative Site
Dijon Cedex, France, 21034
Novartis Investigative Site
Saint-Herblain Cédex, France, 44805
Germany
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Tuebingen, Germany, 72076
Italy
Novartis Investigative Site
Prato, PO, Italy, 59100
Novartis Investigative Site
Candiolo, TO, Italy, 10060
Singapore
Novartis Investigative Site
Singapore, Singapore, 119228
Spain
Novartis Investigative Site
Malaga, Andalucia, Spain, 29010
Novartis Investigative Site
Santiago de Compostela, Galicia, Spain, 15706
Novartis Investigative Site
Madrid, Spain, 28009
Sweden
Novartis Investigative Site
Stockholm, Sweden, SE-171 76
United Kingdom
Novartis Investigative Site
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
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Director: Novartis Investigative Site Novartis Investigative Site
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01271920     History of Changes
Other Study ID Numbers: CAUY922A2109, 2009-015628-27
Study First Received: November 3, 2010
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Netherlands: Dutch Health Care Inspectorate
Singapore: Health Sciences Authority
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency

Keywords provided by Novartis:
Trastuzumab-refractory
advanced HER2-positive breast cancer,
Hsp90,
2nd or 3rd line treatment

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Trastuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014