Panobinostat and Letrozole in Treating Patients With Metastatic Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Genetic: RNA analysisGenetic: microarray analysisGenetic: reverse transcriptase-polymerase chain reactionOther: enzyme-linked immunosorbent assayOther: immunohistochemistry staining methodOther: laboratory biomarker analysis
- Registration Number
- NCT01105312
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description panobinostat (LBH589) and letrozole RNA analysis 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. panobinostat (LBH589) and letrozole microarray analysis 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. panobinostat (LBH589) and letrozole reverse transcriptase-polymerase chain reaction 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. panobinostat (LBH589) and letrozole enzyme-linked immunosorbent assay 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. panobinostat (LBH589) and letrozole immunohistochemistry staining method 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. panobinostat (LBH589) and letrozole laboratory biomarker analysis 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. panobinostat (LBH589) and letrozole letrozole 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. panobinostat (LBH589) and letrozole panobinostat 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.
- Primary Outcome Measures
Name Time Method Response Rate (Phase II) from baseline up to 5 years post-registration 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)Maximum-tolerated Dose (Phase I) Up to 2.5 months 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.
- Secondary Outcome Measures
Name Time Method Survival Time (Phase II) from baseline up to 5 years post-registration Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier
Time-to-disease Progression (Phase II) from baseline up to 6 months Time-to-disease progression (TTP) is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of TTP will be estimated using the method of Kaplan-Meier. Progression is defined as at least one of the following:
1. At least one new malignant lesion or a lymph node whose short axis has increased to \>1.5 cm
2. At least a 20% increase in the sum of diameters of target lesions taking as reference the MSD. In addition, the sum must also demonstrate an absolute increase of at least 0.5 cmProgression-free Survival (Phase II) from baseline up to 6 months Progression-free survival (PFS) is defined as the time from registration to progression or death due to any cause. PFS at 6 months will be estimated. The distribution of PFS will be estimated using the method of Kaplan-Meier.
Duration of Response (Phase II) from baseline up to 5 years post-registration Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.
Time to Treatment Failure from baseline up to 5 years post-registration Time to treatment failure (TTF) is defined as the time from the date of registration to the date at which the patient is removed from treatment due to progression, unacceptable adverse events, or refusal. The distribution of TTF will be estimated using the method of Kaplan-Meier
Confirmed Response Rate (Phase I) from baseline up to 5 years A confirmed response is defined to be a CR or PR (as determined by RECIST 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. The number of confirmed responses will be reported here.
Clinical Benefit Rate from baseline up to 6 months Clinical benefit rate will be estimated by the total number of patients with an objective status of CR, PR, or SD for duration of at least 6 months divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true clinical benefit rate will be calculated.
Trial Locations
- Locations (170)
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
Contra Costa Regional Medical Center
🇺🇸Martinez, California, United States
El Camino Hospital Cancer Center
🇺🇸Mountain View, California, United States
Bay Area Breast Surgeons, Incorporated
🇺🇸Oakland, California, United States
CCOP - Bay Area Tumor Institute
🇺🇸Oakland, California, United States
Larry G Strieff MD Medical Corporation
🇺🇸Oakland, California, United States
Tom K Lee, Incorporated
🇺🇸Oakland, California, United States
Doctors Medical Center - San Pablo Campus
🇺🇸San Pablo, California, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Scroll for more (160 remaining)Mayo Clinic Scottsdale🇺🇸Scottsdale, Arizona, United States