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

NCT01271920 | Completed Phase 1

• 2 other identifiers: CAUY922A21092009-015628-27
• Study Type: interventional
• Target: 45
• Locations: 8 countries
• Sites: 16

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unacceptable toxicity, death, or discontinuation from the study for any other reason, such as patient refusal, withdrawn consent, lost to follow-up or investigator decision.

Conditions

Advanced HER2-positive Breast Cancer

Keywords

Trastuzumab-refractory; advanced HER2-positive breast cancer,; Hsp90,; 2nd or 3rd line treatment

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (1)

AUY922 + Trastuzumab

EXPERIMENTAL

Drug: AUY922; Drug: Trastuzumab

Interventions

AUY922 DRUG

AUY922 + Trastuzumab

Trastuzumab DRUG

AUY922 + Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (16)

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, 72703, United States

Location

Novartis Investigative Site

Dijon, 21034, France

Location

Novartis Investigative Site

Saint-Herblain Cédex, 44805, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Tübingen, 72076, Germany

Location

Novartis Investigative Site

Prato, PO, 59100, Italy

Location

Novartis Investigative Site

Candiolo, TO, 10060, Italy

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Stockholm, SE-171 76, Sweden

Location

Novartis Investigative Site

Birmingham, B15 2TT, United Kingdom

Location

Novartis Investigative Site

Leicester, LE1 5WW, United Kingdom

Location

Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

Location

Novartis Investigative Site

Oxford, OX2 6HE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 27129177 RESULT

Related Links

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

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis Investigative Site

  Novartis Investigative Site

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2010
• First Posted: January 7, 2011
• Study Start: September 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 8, 2020

Record last verified: 2017-02

Locations

DE (2); IT (2); SE (1); SG (1); ES (3); FR (2); GB (4); US (1)