Breast Cancer
Conditions
Brief summary
The purpose of the study is to assess the benefit of oral panobinostat monotherapy given to women with HER2-negative locally recurrent or metastatic breast cancer.
Detailed description
This was a phase II, open label, multi-centre, two-arm, two-stage design, international study of oral panobinostat in women with HER2-negative locally recurrent or metastatic breast cancer. In the first stage of the trial, 21 evaluable patients HR+ (ER+ and/or PgR+), HER2-negative, were to be treated (Arm I); if less than 3 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective. In the other arm, 27 evaluable patients HR- (ER- and PgR-), HER2-negative, were to be treated (Arm II); if less than 2 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective. Given these protocol conditions, the study was stopped in Arm II due to low recruitment as there was insufficient data available to draw conclusions regarding efficacy in that arm. It should also be noted that only one response was observed in this group.. In Arm I, among the 25 evaluable patients, the study did not achieve the required number of tumor responses to allow enrolment to continue. As such the protocol was amended to stop enrolment and remove analysis of the initially planned secondary objectives (Progression Free Survival and Overall Survival) considering the small study sample size. The patients already included were given the option to continue in the study until they reached their planned end-of-study visit.
Interventions
DRUGPanobinostat
Hard gelatine capsule - 5mg and 20mg
Sponsors
Translational Research in Oncology
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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 (14 days) prior to registration * Histologically or cytologically confirmed breast cancer with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent. * Measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines * HER2-negative patients by local laboratory testing (IHC 0 or 1+ staining, IHC 2+ staining but in situ hybridization negative, or in situ hybridization negative). * ER and PgR testing from a local laboratory is required prior to patient registration * For Arm I: at least two lines of prior endocrine therapy (in adjuvant and/or metastatic settings) are required. Up to two prior cytotoxic chemotherapies are allowed in the metastatic setting (prior adjuvant and neoadjuvant chemotherapy is allowed). * For Arm II: up to 2 prior cytotoxic chemotherapy regimens for treatment of metastatic or locally recurrent breast cancer are allowed. * Complete radiological tumor measurement within 4 weeks (28 days) prior to registration: * Chest: CT scan with intravenous contrast if the contrast is not medically contraindicated or MRI * Abdomen: CT scan with intravenous or oral contrast if the contrast is not medically contraindicated or MRI * Brain: CT scan or MRI * Bone: Whole body Bone Scintigraphy * Patients must meet the following laboratory criteria within 2 weeks (14 days) prior to registration: * Hematology * Neutrophil count of \> 1200/mm3 * Platelet count of \> 100,000/mm3 * Hemoglobin ≥ 90 g/L * Biochemistry * AST/SGOT and 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, and calcium within normal limits for the institution * Serum albumin ≥ LLN or 30g/L * Clinically euthyroid function (TSH and free T4). (Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism). * LVEF assessment (2-D echocardiogram or MUGA scan) performed within 6 weeks prior to registration, showing a LVEF value \> 50% * Electrocardiogram performed within 1 week prior to registration (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 registration and agree to appropriate method of pregnancy prevention. * Patient should have an archival tumor sample available for confirmation of HER2, Estrogen and Progesterone status by the central lab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | 6 years and 2 months | The assessment of overall response (OR) is based on the response of target lesion, of non-target lesion, and on presence of new lesions (RECIST criteria version 1.0 using imaging techniques; as per investigator assessment). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ER+ and/or PgR+ (Arm I) Panobinostat - LBH589: hard gelatine capsule - 5mg and 20mg | 33 |
| ER- and PgR- (Arm II) Panobinostat - LBH589: hard gelatine capsule - 5mg and 20mg | 21 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No treatment (elevated liver enzymes) | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | ER+ and/or PgR+ (Arm I) | ER- and PgR- (Arm II) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 3 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 18 Participants | 40 Participants |
| Age, Continuous | 60.3 years STANDARD_DEVIATION 9.5 | 52.8 years STANDARD_DEVIATION 10.7 | 57.4 years STANDARD_DEVIATION 10.5 |
| Ethnicity Hispanic or Latino | 2 participants | 3 participants | 5 participants |
| Ethnicity Not Hispanic or Latino | 31 participants | 18 participants | 49 participants |
| Menopausal Status Postmenopausal | 33 participants | 16 participants | 49 participants |
| Menopausal Status Premenopausal | 0 participants | 5 participants | 5 participants |
| Race/Ethnicity, Customized Race - Asian | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Race - Black or African American | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Race - White | 31 participants | 20 participants | 51 participants |
| Region of Enrollment Belgium | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Canada | 4 participants | 6 participants | 10 participants |
| Region of Enrollment France | 5 participants | 1 participants | 6 participants |
| Region of Enrollment Ireland | 10 participants | 1 participants | 11 participants |
| Region of Enrollment United Kingdom | 2 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 11 participants | 10 participants | 21 participants |
| Sex: Female, Male Female | 33 Participants | 21 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 32 | 20 / 20 |
| serious Total, serious adverse events | 12 / 32 | 8 / 20 |
Outcome results
Primary
Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR.
The assessment of overall response (OR) is based on the response of target lesion, of non-target lesion, and on presence of new lesions (RECIST criteria version 1.0 using imaging techniques; as per investigator assessment).
Time frame: 6 years and 2 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ER+ and/or PgR+ (Arm I) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Partial Response | 1 participants |
| ER+ and/or PgR+ (Arm I) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Progressive Disease | 14 participants |
| ER+ and/or PgR+ (Arm I) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Stable Disease / Incompete Response | 13 participants |
| ER+ and/or PgR+ (Arm I) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Missing | 5 participants |
| ER+ and/or PgR+ (Arm I) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Complete Response | 0 participants |
| ER- and PgR- (Arm II) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Missing | 2 participants |
| ER- and PgR- (Arm II) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Complete Response | 1 participants |
| ER- and PgR- (Arm II) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Partial Response | 0 participants |
| ER- and PgR- (Arm II) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Stable Disease / Incompete Response | 4 participants |
| ER- and PgR- (Arm II) | Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. | Progressive Disease | 14 participants |