Study of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer

NCT00777049 | Completed Phase 2 Results

• 1 other identifier: TRIO 017
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the benefit of oral panobinostat monotherapy given to women with HER2-negative locally recurrent or metastatic breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR.

  The assessment of overall response (OR) is based on the response of target lesion, of non-target lesion, and on presence of new lesions (RECIST criteria version 1.0 using imaging techniques; as per investigator assessment).

  6 years and 2 months

Study Arms (2)

ER+ and/or PgR+ (Arm I)

EXPERIMENTAL

Panobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle.

Drug: Panobinostat

ER- and PgR- (Arm II)

EXPERIMENTAL

Panobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle.

Drug: Panobinostat

Interventions

Panobinostat DRUG

Hard gelatine capsule - 5mg and 20mg

Also known as: LBH589

ER+ and/or PgR+ (Arm I); ER- and PgR- (Arm II)

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained prior to any study-related procedures
• Women ≥ 18 years old
• Patients with an ECOG performance status of ≤ 2 assessed within 2 weeks (14 days) prior to registration
• Histologically or cytologically confirmed breast cancer with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
• Measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines
• HER2-negative patients by local laboratory testing (IHC 0 or 1+ staining, IHC 2+ staining but in situ hybridization negative, or in situ hybridization negative).
• ER and PgR testing from a local laboratory is required prior to patient registration
• For Arm I: at least two lines of prior endocrine therapy (in adjuvant and/or metastatic settings) are required. Up to two prior cytotoxic chemotherapies are allowed in the metastatic setting (prior adjuvant and neoadjuvant chemotherapy is allowed).
• For Arm II: up to 2 prior cytotoxic chemotherapy regimens for treatment of metastatic or locally recurrent breast cancer are allowed.
• Complete radiological tumor measurement within 4 weeks (28 days) prior to registration:
• Chest: CT scan with intravenous contrast if the contrast is not medically contraindicated or MRI
• Abdomen: CT scan with intravenous or oral contrast if the contrast is not medically contraindicated or MRI
• Brain: CT scan or MRI
• Bone: Whole body Bone Scintigraphy
• Patients must meet the following laboratory criteria within 2 weeks (14 days) prior to registration:

You may not qualify if:

• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to registration and agree to appropriate method of pregnancy prevention.
• Patient should have an archival tumor sample available for confirmation of HER2, Estrogen and Progesterone status by the central lab.
• Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• Patients who need valproic acid for any other medical condition during the study or within 5 days prior to first panobinostat treatment
• Patients who have received prior systemic anti-cancer therapy (cytotoxic chemotherapy, endocrine therapy, targeted therapy, monoclonal antibody or biologic therapy) or investigational agent within the last 4 weeks prior to registration (6 weeks for nitrosoureas and mitomycin; 2 weeks for capecitabine)
• Patients who have received prior radiotherapy to ≥ 25% of the bone marrow within the last 4 weeks prior to registration; local radiotherapy is allowed however all recently irradiated lesions should not be included in the measurable disease assessment.
• Patients who have received prior investigational agents within the last 4 weeks prior to registration
• Patients with unresolved diarrhea ≥CTCAE grade 1
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
• History of cardiac dysfunction including any one of the following:
• Complete left bundle branch block or obligate use of a cardiac pacemaker or congenital long QT syndrome or history or presence of ventricular tachyarrhythmias or clinically significant resting bradycardia (\<50 beats per minute) or QTcF \> 450 msec on screening ECG or right bundle branch block and left anterior hemiblock (bifascicular block)
• Previous history angina pectoris or acute MI within 6 months of registration
• Congestive Heart Failure (New York Heart Association functional classification III-IV)
• History of unexplained syncope
• Other clinically significant heart disease (e.g. cardiomyopathy, cardiac artery disease, uncontrolled hypertension, or history of poor compliance with an antihypertensive regimen)

Sponsors & Collaborators

• Translational Research in Oncology: lead

Study Sites (1)

UCLA

Los Angeles, California, 90095-1678, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

In Arm II, low recruitment resulted in insufficient data (and enrollment was stopped). In Arm I, the required number of tumor responses was not reached. Unable to determine efficacy (small sample); secondary objectives also removed from the protocol.

Results Point of Contact

• Title: Valérie Bee-Muntenau, Director of Project Management
• Organization: Translational Research in Oncology (TRIO)

Valerie.Bee@trioncology.org

+33 1 58 10 09 09

Study Officials

• Sara Hurvitz, MD

  University of California, Los Angeles

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2008
• First Posted: October 22, 2008
• Study Start: February 1, 2009
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: July 15, 2016
• Results First Posted: July 15, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)