Clinical trial NCT01105312
Conditions: Breast Cancer
Keywords: male breast cancer estrogen receptor-negative breast cancer estrogen receptor-positive breast cancer HER2-negative breast cancer HER2-positive breast cancer progesterone receptor-negative breast cancer progesterone receptor-positive breast cancer triple-negative breast cancer recurrent breast cancer stage IV breast cancer
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2010-09-01; Completion date: 2013-09-03
Enrollment: 28 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Detailed description:
OBJECTIVES:

Primary Objectives

* To determine the maximum-tolerated dose of panobinostat in combination with letrozole in patients with metastatic breast cancer. (Phase I)
* To determine the safety of this regimen in these patients. (Phase I)
* To assess the confirmed response rate and safety profile of this regimen in patients with triple-negative disease. (Phase II)

Secondary Objectives

* To assess the therapeutic effects of this regimen in these patients. (Phase I)
* To examine the duration of response, clinical benefit rate, and time to treatment failure in patients treated with this regimen. (Phase II)
* To examine the time to progression, progression-free survival, and overall survival of patients treated with this regimen. (Phase II)
* To examine the estrogen, progesterone, and HER2 status of tumor at primary compared to metastatic tissue, and possibly after treatment. (exploratory)
* To bank paraffin-embedded tissue blocks/slides and blood products for future studies. (exploratory)
* To determine expression levels of biomarkers of treatment response (i.e., ER, PR, aromatase, NFkappaB, Ki67, and Caspase 3) in accessible tumors pre- and post-therapy via immunohistochemistry. (exploratory)
* To determine whether ELISA for KLK11 in serum can be used as marker of activity of letrozole and LBH589. (exploratory) The Phase I portion of this study closed and the Phase II portion of the study opened as per NCCTG Addendum 6, effective January 23, 2012.

OUTLINE: This is a multicenter, phase I dose-escalation study of panobinostat followed by a phase II study. (The Phase I portion of this study closed and the Phase II portion of the study opened as per NCCTG Addendum 6, effective January 23, 2012.)

Patients receive oral panobinostat once daily on days 1, 3, and 5 in weeks 1-4 and oral letrozole once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Tumor tissue and blood samples are collected and banked for future biomarker and other analysis. Samples are also analyzed for biomarkers utilizing immunohistochemistry, microarray, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA).

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Arms: arm 1: 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.
Interventions: intervention 1: letrozole intervention 2: panobinostat intervention 3: RNA analysis intervention 4: microarray analysis intervention 5: reverse transcriptase-polymerase chain reaction intervention 6: enzyme-linked immunosorbent assay intervention 7: immunohistochemistry staining method intervention 8: laboratory biomarker analysis
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None

Protocol documents: