Brief Summary

RATIONALE: Panobinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving panobinostat together with letrozole may be an effective treatment for breast cancer. PURPOSE: This phase I/II trial is studying the side effects and best dose of panobinostat when given together with letrozole and to see how well it works in treating patients with metastatic breast cancer.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for phase_1 breast-cancer

Timeline

Completed

Started Sep 2010

Geographic Reach

1 country

172 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

3 years study duration

First Submitted

Initial submission to the registry

April 15, 2010

Completed

1 day until next milestone

First Posted

Study publicly available on registry

April 16, 2010

Completed

5 months until next milestone

Study Start

First participant enrolled

September 1, 2010

Completed

2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2013

Completed

1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

September 3, 2013

Completed

3.8 years until next milestone

Results Posted

Study results publicly available

June 27, 2017

Completed

Last Updated

June 27, 2017

Status Verified

May 1, 2017

Enrollment Period

2.9 years

First QC Date

April 15, 2010

Results QC Date

February 28, 2017

Last Update Submit

May 23, 2017

Conditions

Breast Cancer

Keywords

male breast cancerestrogen receptor-negative breast cancerestrogen receptor-positive breast cancerHER2-negative breast cancerHER2-positive breast cancerprogesterone receptor-negative breast cancerprogesterone receptor-positive breast cancertriple-negative breast cancerrecurrent breast cancerstage IV breast cancer

Outcome Measures

Primary Outcomes (2)

Maximum-tolerated Dose (Phase I)
MTD is defined as the dose level below the lowest dose that induces dose limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6\> new patients). If dose-limiting toxicity (DLT) is not seen in any of the 3 patients, 3 new patients will be accrued and treated at the next higher dose level. If DLT are seen in 2 or 3 of 3 patients treated at a given dose level, then the next 3 patients will be treated at the next lower dose level, if only 3 patients were enrolled and treated at this lower dose level. The number of DLT's will be reported here.
Up to 2.5 months
Response Rate (Phase II)
A confirmed response is defined to be a CR or PR (as determined by RECIST (version 1.1 criteria) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Response will be evaluated using all cycles of treatment. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response. A CR is defined as: All of the following must be true: 1. Disappearance of all non-nodal target lesions 2. Each target lymph node must have reduction in short axis to \<1.0 cm A PR is defined as: At least a 30% decrease in the sum of the longest diameters of the non-nodal target lesions and the short axes of the target lymph nodes taking as reference the BSD (Section 11.41)
from baseline up to 5 years post-registration

Secondary Outcomes (7)

Survival Time (Phase II)
from baseline up to 5 years post-registration
Time-to-disease Progression (Phase II)
from baseline up to 6 months
Progression-free Survival (Phase II)
from baseline up to 6 months
Duration of Response (Phase II)
from baseline up to 5 years post-registration
Clinical Benefit Rate
from baseline up to 6 months
+2 more secondary outcomes

Study Arms (1)

panobinostat (LBH589) and letrozole

EXPERIMENTAL

Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered LBH589 PO, 3 days per week for a total of 4 weeks. Patients will also be administered letrozole 2.5 mg PO Days 1-28 every 4 weeks. There are two phases of the study. The first phase determines the maximum tolerated dose for LBH589 in combination with letrozole. The second phase is to assess and confirm the response rate and safety profile of LBH589 in combination with letrozole.

Drug: letrozoleDrug: panobinostatGenetic: RNA analysisGenetic: microarray analysisGenetic: reverse transcriptase-polymerase chain reactionOther: enzyme-linked immunosorbent assayOther: immunohistochemistry staining methodOther: laboratory biomarker analysis