Study of Panobinostat Monotherapy in Women With v-ERB-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2) Positive Locally Recurrent or Metastatic Breast Cancer

NCT00777335 | Terminated Phase 2 Results

• 1 other identifier: TRIO 016
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to assess the benefit of panobinostat monotherapy given either orally or i.v. to women with HER2-positive locally recurrent or metastatic breast cancer

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response (OR) Rate (as Determined by the Investigator): the Number of Patients Assigned to a Treatment Arm With a Confirmed Best Response of Complete Response(CR) or Partial Response (PR).

  The assessment of OR is based on the response of target lesion, of non-target lesion and on presence of new lesions (RECIST Criteria (V1.0)-assessed by CT scan spiral and bone scan) * CR:Disappearance of all target lesions * PR:\>=30% increase in the sum of the longest diameter (SLD),taking as reference the nadir SLD * Progressive Disease (PD):\>=20% increase in the SLD, taking as reference the nadir SLD, or the appearance of one or more new lesions * Stable Disease(SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the nadir SLD

  At screening, every 2 cycles (i.e. 6 weeks) during the first 6 cycles, every 3 cycles (i.e. 9 weeks) during the subsequent cycles and at the End of Treatment (EOT) visit. After the EOT, the tumor assessments should be performed every 9 weeks.

Secondary Outcomes (1)

• Corrected QT Interval Fridericia's Formula (QTcF)

  Panobinostat intra-venous (i.v.): All cycles pre-dose measurements. For cycles 1 and 2, post-dose measurements as well. / Panobinostat oral: Pre-dose and post-dose measurements for all cycles. Note: each cycle = 3 weeks

Study Arms (2)

Panobinostat i.v.

EXPERIMENTAL

Drug: Panobinostat - LBH589

Panobinostat oral

EXPERIMENTAL

Drug: Panobinostat - LBH589

Interventions

Panobinostat - LBH589 DRUG

Solution for infusion - 25mg/5ml

Panobinostat i.v.

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 prior to randomization
• Histologically or cytologically confirmed invasive breast carcinoma with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines
• HER2-positive breast cancer patients by local laboratory testing
• Prior trastuzumab-containing regimen (in neoadjuvant and/or adjuvant and/or metastatic settings) regardless of whether trastuzumab was given as monotherapy or in combination with chemotherapy. Any number of prior trastuzumab regimens is acceptable. Additional treatment with lapatinib after or before trastuzumab treatment is permitted, but not mandatory.
• Radiological evidence of relapse or disease progression while on trastuzumab (or lapatinib) or within 12 months of the last dose of adjuvant trastuzumab.
• Complete radiology and tumor assessment within 4 weeks prior to randomization:
• Chest: Computed Tomography(CT) scan with intravenous contrast if the contrast is not medically contraindicated or Magnetic Resonance Imaging(MRI)
• Abdomen: CT scan with intravenous and oral contrast if the contrast is not medically contraindicated or MRI
• Brain: CT scan or MRI
• Bone: Whole body Bone Scintigraphy
• Up to 2 prior cytotoxic chemotherapy regimens, in addition to neo-adjuvant and adjuvant, for treatment of metastatic or locally recurrent breast cancer (including those cytotoxic chemotherapy treatments in combination with trastuzumab and/or lapatinib)
• Patients must meet the following laboratory criteria within 2 weeks (14 days) prior to randomization:

You may not qualify if:

• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to randomization and agree to appropriate method of pregnancy prevention
• Prior Histone Deacetylase(HDAC),Deacetylase(DAC), Heat Shock Protein 90 (HSP90) inhibitors or valproic acid for the treatment of cancer
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Patients who have received prior chemotherapy or investigational agent within the last 4 weeks prior to randomization (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 randomization; 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 randomization
• Patients with unresolved diarrhea ≥CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) 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 necessity for a permanent 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 electrocardiogram(ECG) or right bundle branch block and left anterior hemiblock (bifascicular block)
• Previous history angina pectoris or acute myocardial infarction(MI) within 6 months of randomization
• Congestive heart failure (New York Heart Association functional classification III-IV)
• Other clinically significant heart disease (e.g. cardiomyopathy, cardiac artery disease, uncontrolled hypertension, or history of poor compliance with an antihypertensive regimen)
• Acute or chronic liver or renal disease
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol

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

The recruitment rate has shown to be very low worldwide. In total, 4 patients only were recruited, instead of the 132 initially targeted. Due to the very small number of subjects randomized in this study, only descriptive analyses have been made.

Results Point of Contact

• Title: Dr. Richard Finn
• Organization: University of California Los Angeles (UCLA) / Cancer International Research Group (CIRG) (Translational Research in Oncology TRIO) Inc.

RFinn@mednet.ucla.edu

+ 1 310 586 2091

Study Officials

• Richard Finn, 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: 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: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: November 24, 2015
• Results First Posted: April 10, 2012

Record last verified: 2015-10

Locations

US (1)