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A Randomized Phase II, Open-label Multicenter Trial of Panobinostat Monotherapy in Women With HER2 Positive Locally Recurrent or Metastatic Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Randomized Phase II, Open-label Multicenter Trial of Panobinostat Monotherapy in Women With HER2 Positive Locally Recurrent or Metastatic Breast Cancer

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 prior to

- 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)

- 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

- Patients must meet the following laboratory criteria within 2 weeks (14 days) prior
to randomization:

- Hematology

- Neutrophil count of > 1200/mm3

- Platelet count of > 100,000/mm3

- Hemoglobin ≥ 90 g/L

- Biochemistry

- Aspartate aminotransferase/glutamic oxaloacetic transaminase (AST/SGOT) and alanine
aminotransferase/glutamic pyruvic transaminase(ALT/SGPT) ≤ 2.5 x upper limit of
normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease

- 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, total calcium (corrected for serum
albumin) or ionized calcium within normal limits for the institution

- Serum albumin ≥ Lower Limit of Normal(LLN) or 30g/L

- Clinically euthyroid function (thyroid-stimulating hormone (TSH) and free T4).
(Patients are permitted to receive thyroid hormone supplements to treat underlying

- Left Ventricular Ejection Fraction(LVEF) assessment (2-D echocardiogram or Multiple
Uptake Gated Acquisition Scan(MUGA) scan) performed within 6 weeks prior to
randomization, showing a LVEF value > 50%

- Electrocardiogram performed within 1 week prior to randomization (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 randomization and agree to appropriate method of pregnancy

Exclusion Criteria:

- 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

- 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)

- 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 myocardial infarction(MI) within 6 months
of randomization

- Congestive heart failure (New York Heart Association functional classification

- 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

- 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 bisphosphonates unless if initiated prior to study entry (at least 4 weeks
before study randomization)

- Pregnant (i.e., positive beta-human chorionic gonadotropin test) or breast feeding

- 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 90 days after last dose of study

- Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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).

Outcome Description:

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

Outcome Time Frame:

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.

Safety Issue:


Principal Investigator

Richard Finn, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, Los Angeles


United States: Food and Drug Administration

Study ID:

TRIO 016



Start Date:

February 2009

Completion Date:

March 2010

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms
  • Leukemia, Erythroblastic, Acute



UCLA Los Angeles, California  90095