Breast CancerPhase 2NCT00777335

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

A Phase 2 study testing Panobinostat - LBH589 in people with Breast Cancer, run by Translational Research in Oncology at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer
What is being tested?: Panobinostat - LBH589
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: 1 siteUnited States
Study dates: Feb 2009to Mar 2010
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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:
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 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, 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 hypothyroidism).
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 prevention

Who cannot join

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

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

Trial locations and contacts

1 site in 1 country.

United States1 site

UCLA
Los Angeles, California, 90095-1678

Other trials in United States

About this study

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

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
Being tested: Panobinostat - LBH589
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Panobinostat - LBH589Drug
Solution for infusion - 25mg/5ml
Panobinostat - LBH589Drug
Hard gelatine capsules - 5mg and 20 mg

Study groups in NCT00777335
Study group	Role	What they receive
Panobinostat i.v.	Experimental	Not described Receives: Drug: Panobinostat - LBH589
Panobinostat oral	Experimental	Not described Receives: Drug: Panobinostat - LBH589

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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)
Prolonged QTcF: QTcF >450 msec and increase of baseline on greater than or equal to 60 msec.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2009Mar 2010

First posted22 Oct 2008 (estimated)
Study startFeb 2009
Primary completionMar 2010
Study completionMar 2010

Why it stopped: Very low recruitement rate.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00777335
Sponsor's protocol ID: TRIO 016
Status last verified: Oct 2015
First submitted: 21 Oct 2008
Last updated: 24 Nov 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 24 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Phase II, Open-label Multicenter Trial of Panobinostat Monotherapy in Women With HER2 Positive Locally Recurrent or Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT00777335
Acronym / sponsor ID: TRIO 016
Conditions: Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Very low recruitement rate.
Enrolment: 4 participants (actual)
Lead sponsor: Translational Research in OncologyUniversity, hospital or other
Study start: Feb 2009
Primary completion: Mar 2010 (actual)
Study completion: Mar 2010 (actual)
First posted: 22 Oct 2008 (estimated)
Results: Posted 10 Apr 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Panobinostat i.v.	Experimental	Drug: Panobinostat - LBH589
Panobinostat oral	Experimental	Drug: Panobinostat - LBH589

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (29 listed)

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

Key exclusion criteria (23 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Panobinostat - LBH589Solution for infusion - 25mg/5ml	Drug	Panobinostat i.v.
Panobinostat - LBH589Hard gelatine capsules - 5mg and 20 mg	Drug	Panobinostat oral

Primary outcome

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).
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.
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

1 secondary outcome

Corrected QT Interval Fridericia's Formula (QTcF)
Time frame: 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

Results and safety

Results posted to the registry on 10 Apr 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Panobinostat Intra-venous (i.v.)	2	2
Panobinostat Oral	2	2

Primary outcome: 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).

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.. Number. Unit: participants

Measure	Panobinostat Intra-venous (i.v.) n = 2	Panobinostat Oral n = 2
Progressive Disease (PD)	2	1
Stable Disease (SD)	0	1
Complete Response (CR)	0	0
Partial Reponse (PR)	0	0

1 secondary outcome is reported in the full results.

Adverse events

Time frame: The period for collection and reporting of adverse events extends from the time the patient signs the informed consent form (even if the event is not considered to be related to the study drug) until 28 days after the last receipt of the study treatment.. Other adverse events reported at 3.0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Panobinostat Intra-venous (i.v.)	1 of 2 (50%)	2 of 2 (100%)	Not reported
Panobinostat Oral	0 of 2 (0%)	2 of 2 (100%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Richard Finn, MD study chair

University of California, Los Angeles

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panobinostat - LBH589 in people with Breast Cancer, run by Translational Research in Oncology at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary 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). (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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00777335.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2015.