Trial Outcomes & Findings for Panobinostat and Letrozole in Treating Patients With Metastatic Breast Cancer (NCT NCT01105312)
NCT ID: NCT01105312
Last Updated: 2017-06-27
Results Overview
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.
COMPLETED
PHASE1/PHASE2
28 participants
Up to 2.5 months
2017-06-27
Participant Flow
Participant milestones
| Measure |
Phase II
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level One
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
16
|
6
|
6
|
|
Overall Study
COMPLETED
|
13
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
3
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Panobinostat and Letrozole in Treating Patients With Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Phase II
n=16 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level One
n=6 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
n=6 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Age, Continuous
|
60.5 years
n=5 Participants
|
66 years
n=7 Participants
|
63 years
n=5 Participants
|
62.5 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
16 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
28 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 2.5 monthsPopulation: All 12 phase I patients were eligible and analyzed for MTD.
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.
Outcome measures
| Measure |
Phase I: Dose Level One
n=6 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
n=6 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Maximum-tolerated Dose (Phase I)
|
1 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: from baseline up to 5 years post-registrationPopulation: 13 of the 16 patients enrolled were eligible, treated, and analyzed for this endpoint.
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)
Outcome measures
| Measure |
Phase I: Dose Level One
n=13 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Response Rate (Phase II)
|
0 percentage of participants
Interval 0.0 to 24.7
|
—
|
SECONDARY outcome
Timeframe: from baseline up to 5 years post-registrationPopulation: 13 of the 16 phase II patients were eligible, treated, and analyzed.
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
Outcome measures
| Measure |
Phase I: Dose Level One
n=13 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Survival Time (Phase II)
|
16.1 months
Interval 13.4 to
The data is skewed due to small sample size (insufficient number of participants with events)
|
—
|
SECONDARY outcome
Timeframe: from baseline up to 6 monthsPopulation: 13 of the 16 phase II patients were eligible, treated, and analyzed.
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 cm
Outcome measures
| Measure |
Phase I: Dose Level One
n=13 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Time-to-disease Progression (Phase II)
|
2.1 months
Interval 1.5 to
The data is skewed due to small sample size (insufficient number of participants with events)
|
—
|
SECONDARY outcome
Timeframe: from baseline up to 6 monthsPopulation: 13 of the 16 phase II patients were eligible, treated, and analyzed.
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.
Outcome measures
| Measure |
Phase I: Dose Level One
n=13 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Progression-free Survival (Phase II)
|
2.1 months
Interval 1.5 to
The data is skewed due to small sample size (insufficient number of participants with events)
|
—
|
SECONDARY outcome
Timeframe: from baseline up to 5 years post-registrationPopulation: 13 of the 16 phase II patients were treated and analyzed
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.
Outcome measures
| Measure |
Phase I: Dose Level One
n=13 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Duration of Response (Phase II)
|
NA months
There were no responders and thus no data to assess this endpoint.
|
—
|
SECONDARY outcome
Timeframe: from baseline up to 6 monthsPopulation: 13 of the 16 phase II patients were eligible, treated, and analyzed.
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.
Outcome measures
| Measure |
Phase I: Dose Level One
n=13 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Clinical Benefit Rate
|
0 percentage of participants
Interval 0.0 to 24.7
|
—
|
SECONDARY outcome
Timeframe: from baseline up to 5 years post-registrationPopulation: 13 of the 16 phase II patients were eligible, treated, and analyzed.
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
Outcome measures
| Measure |
Phase I: Dose Level One
n=13 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Time to Treatment Failure
|
2 months
Interval 1.1 to
The data is skewed due to small sample size (insufficient number of participants with events)
|
—
|
SECONDARY outcome
Timeframe: from baseline up to 5 yearsPopulation: All 12 eligible phase I patients were treated and analyzed.
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.
Outcome measures
| Measure |
Phase I: Dose Level One
n=6 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
n=6 Participants
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|
|
Confirmed Response Rate (Phase I)
|
0 Participants
|
2 Participants
|
Adverse Events
Phase II
Phase I: Dose Level One
Phase I: Dose Level Two
Serious adverse events
| Measure |
Phase II
n=16 participants at risk
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level One
n=6 participants at risk
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
n=6 participants at risk
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|---|
|
Infections and infestations
Bladder infection
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Infections and infestations
Lung infection
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Fracture
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Platelet count decreased
|
18.8%
3/16 • Number of events 3
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
White blood cell decreased
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/16
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/16
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
Other adverse events
| Measure |
Phase II
n=16 participants at risk
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level One
n=6 participants at risk
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 20 mg 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.
|
Phase I: Dose Level Two
n=6 participants at risk
Each patient will receive panobinostat (LBH589) and letrozole. Patients will be administered 30 mg 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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhea
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
12.5%
2/16 • Number of events 3
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
General disorders
Edema limbs
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Fatigue
|
12.5%
2/16 • Number of events 5
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 6
|
|
Infections and infestations
Bladder infection
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Alanine aminotransferase increased
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Investigations
Blood bilirubin increased
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
|
Investigations
Creatinine increased
|
31.2%
5/16 • Number of events 12
|
50.0%
3/6 • Number of events 5
|
66.7%
4/6 • Number of events 9
|
|
Investigations
Electrocardiogram QT corrected interval prolonged
|
31.2%
5/16 • Number of events 6
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Neutrophil count decreased
|
25.0%
4/16 • Number of events 8
|
50.0%
3/6 • Number of events 7
|
100.0%
6/6 • Number of events 9
|
|
Investigations
Platelet count decreased
|
56.2%
9/16 • Number of events 15
|
83.3%
5/6 • Number of events 18
|
100.0%
6/6 • Number of events 20
|
|
Investigations
Weight loss
|
6.2%
1/16 • Number of events 3
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
White blood cell decreased
|
31.2%
5/16 • Number of events 9
|
83.3%
5/6 • Number of events 15
|
66.7%
4/6 • Number of events 5
|
|
Metabolism and nutrition disorders
Anorexia
|
12.5%
2/16 • Number of events 3
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Glucose intolerance
|
6.2%
1/16 • Number of events 3
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/16
|
0.00%
0/6
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
6.2%
1/16 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
12.5%
2/16 • Number of events 2
|
50.0%
3/6 • Number of events 5
|
33.3%
2/6 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
37.5%
6/16 • Number of events 8
|
33.3%
2/6 • Number of events 7
|
66.7%
4/6 • Number of events 9
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
16.7%
1/6 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/16
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/16
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/16
|
0.00%
0/6
|
16.7%
1/6 • Number of events 2
|
|
Vascular disorders
Hypertension
|
6.2%
1/16 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Anemia
|
56.2%
9/16 • Number of events 15
|
66.7%
4/6 • Number of events 12
|
33.3%
2/6 • Number of events 2
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/16
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60