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Trial record 1 of 1 for:    TRIO 017
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Study of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00777049
Recruitment Status : Completed
First Posted : October 22, 2008
Results First Posted : July 15, 2016
Last Update Posted : July 15, 2016
Sponsor:
Information provided by (Responsible Party):
Translational Research in Oncology

Tracking Information
First Submitted Date  ICMJE October 21, 2008
First Posted Date  ICMJE October 22, 2008
Results First Submitted Date  ICMJE May 26, 2016
Results First Posted Date  ICMJE July 15, 2016
Last Update Posted Date July 15, 2016
Study Start Date  ICMJE February 2009
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 14, 2016)
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. [ Time Frame: 6 years and 2 months ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 21, 2008)
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. [ Time Frame: Once 21/27 evaluable patients will be treated ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer
Official Title  ICMJE A Phase II, Open-label Multicenter Trial of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer
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.
Detailed Description

This was a phase II, open label, multi-centre, two-arm, two-stage design, international study of oral panobinostat in women with HER2-negative locally recurrent or metastatic breast cancer.

In the first stage of the trial, 21 evaluable patients HR+ (ER+ and/or PgR+), HER2-negative, were to be treated (Arm I); if less than 3 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective. In the other arm, 27 evaluable patients HR- (ER- and PgR-), HER2-negative, were to be treated (Arm II); if less than 2 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective.

Given these protocol conditions, the study was stopped in Arm II due to low recruitment as there was insufficient data available to draw conclusions regarding efficacy in that arm. It should also be noted that only one response was observed in this group.. In Arm I, among the 25 evaluable patients, the study did not achieve the required number of tumor responses to allow enrolment to continue.

As such the protocol was amended to stop enrolment and remove analysis of the initially planned secondary objectives (Progression Free Survival and Overall Survival) considering the small study sample size. The patients already included were given the option to continue in the study until they reached their planned end-of-study visit.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: Panobinostat
Hard gelatine capsule - 5mg and 20mg
Other Name: LBH589
Study Arms  ICMJE
  • Experimental: ER+ and/or PgR+ (Arm I)
    Panobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle.
    Intervention: Drug: Panobinostat
  • Experimental: ER- and PgR- (Arm II)
    Panobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle.
    Intervention: Drug: Panobinostat
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 31, 2015)
54
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2008)
118
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date April 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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:
  • Hematology
  • Neutrophil count of > 1200/mm3
  • Platelet count of > 100,000/mm3
  • Hemoglobin ≥ 90 g/L
  • Biochemistry
  • AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
  • Serum bilirubin ≤ 1.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 mL/min
  • Serum potassium, sodium, magnesium, phosphorus, and calcium within normal limits for the institution
  • Serum albumin ≥ LLN or 30g/L
  • Clinically euthyroid function (TSH and free T4). (Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism).
  • LVEF assessment (2-D echocardiogram or MUGA scan) performed within 6 weeks prior to registration, showing a LVEF value > 50%
  • Electrocardiogram performed within 1 week prior to registration (details about findings on the Electrocardiogram that are not acceptable for participating in the study are reported in the Exclusion criteria section)
  • 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.

Exclusion Criteria:

  • 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)
  • Presence of unstable atrial fibrillation (ventricular response rate >100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
  • 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)
  • Family history of long QT syndrome, unexplained syncope or unexplained sudden death
  • 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
  • Concomitant use of drugs with a risk of causing torsades de pointes where such treatments cannot be discontinued or switched to a different medication prior to starting study drug
  • Brain metastases, unless patient randomized on study at least 90 days from completion of brain radiotherapy and / or surgery without radiologic or functional evidence of progressive brain metastases, and off corticosteroids above the dose of 7.5 mg prednisone or equivalent; No concurrent radiotherapy for brain metastasis is allowed
  • Clinically significant third space fluid accumulation
  • Concurrent biphosphonates unless if initiated prior to study entry (at least 4 weeks before patient registration)
  • Pregnant (i.e., positive beta-human chorionic gonadotropin test) or breast feeding patient
  • Unable to swallow oral medications
  • Not willing to use a double barrier method of non-hormonal birth control. Contraception must be used during the study and for 30 days after last dose of study treatment.
  • Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00777049
Other Study ID Numbers  ICMJE TRIO 017
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Translational Research in Oncology
Study Sponsor  ICMJE Translational Research in Oncology
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Sara Hurvitz, MD University of California, Los Angeles
PRS Account Translational Research in Oncology
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP