Neuroendocrine Tumors
Conditions
Brief summary
This summary will use Panobinostat (LBH589) in patients with neuroendocrine tumors to see how the patient's tumor responds to panobinostat. Additionally, this study will examine how long it takes neuroendocrine tumor patient's cancer to progress while taking the drug and examine the overall survival of patients using panobinostat. Also, the study will examine the toxicity and tolerability of panobinostat in the patient population. Finally, this study will look at the effect of panobinostat on Notch 1 signaling before and after treatment with panobinostat.
Interventions
Panobinostat will be taken once daily at 20 mg three times a week (every Monday, Wednesday, Friday). It will be taken as long as patients are benefiting from treatment.
Sponsors
Novartis Pharmaceuticals
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed, metastatic, low grade neuroendocrine neoplasms. Small cell lung cancers, paragangliomas, and pheochromocytomas are excluded * Must have measurable disease as defined by RECIST * 4 weeks from completion of major surgery, chemotherapy, or other systemic therapy or local liver therapy to study registration. Concurrent octreotide is allowed. * Not allowed to be on concurrent chemotherapy or radiation * 18 years of age or older * ECOG Performance status of equal to or less than 2 * Able to sign and date a written informed consent prior to participation in the study * Baseline MUGA or ECHO must demonstrate LVEF greater than or equal to the lower limit of the institutional normal * Must have the following laboratory criteria: Neutrophil count greater than 1500/mm3, platelet count greater than 100,000/mm3L, hemoglobin greater than or equal to 9 g/dL, AST/SGOT and ALT/SGPT less than or equal to 2.5 x ULN, serum bilirubin less than or equal to 1.5 x ULN, serum creatinine less than or equal to 1.5 x ULN, total serum calcium greater than or equal to LLN, serum potassium greater than or equal to LLN, serum sodium greater than or equal to LLN, serum albumin greater than or equal to LLN or 3g/dl, * Women of child bearing potential must have a negative urine pregnancy test within 72 hours of first administration of study treatment and must be willing to use two methods of contraception * Patients with a history of hypertension must be well controlled (to less than 150/90 mmHg) on a stable regimen of anti-hypertensive therapy
Exclusion criteria
* Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer * Patients who will need valproic acid for any medical condition during the study or within 5 days prior to the first panobinostat treatment * Impaired cardiac function including any of the following: Screening ECG with a QTc greater than 450 msec, patients with congenital long QT syndrome, history of unsustained ventricular tachycardia, any history of ventricular fibrillation or torsades de pointes, bradycardia defined as heart rate less than 50 beats per minutes, patients with a myocardial infarction or unstable angina within 6 months of study entry, congestive heart failure, right bundle branch block or left anterior hemiblock * Uncontrolled hypertension * Unresolved diarrhea greater than CTCAE grade 1 * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat * Other concurrent sever and/or uncontrolled medical conditions * Patients with a history of another primary malignancy that, in the opinion of the investigator, would interfere with the assessment of the primary endpoint of the study * Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C, baseline testing is not required * Any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent * Any medication which may cause QTc prolongation or inducing torsades de pointes * Use of concomitant medications that may interact with panobinostat
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | every 8 weeks, up to 5 years | Confirmed anti-tumor response rate will be validated by the Response Evaluation Criteria in Solid Tumors (RECIST). All participants included in the study will be assessed for response to the proposed panobinostat treatment, even if there are protocol treatment deviations. Each participant will be assigned one of the following categories: complete response, partial response, stable disease, progressive disease, early death from malignant disease, early death from toxicity, early death because of other cause, or unknown. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Toxicities | up to 5 years | Evaluate the toxicity and tolerability of panobinostat in the patient population |
| Evaluate the Time to Progression for Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat | Up to 5 years | — |
| Delineate the Expression of Notch 1 in Neuroendocrine Tumor Samples Before and During Treatment With Panobinostat | Pre-treatment and up to week 12 | The expression of Notch 1 in neuroendocrine tumor samples will be evaluated prior to Cycle 1 Day 1 dose and at the end of Cycle 2 of treatment of treatment. |
| Evaluate the Overall Survival of Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat | Up to 5 years | — |
Countries
United States
Participant flow
Recruitment details
This study actively recruited from April 2010 through May 2011 at a large cancer center in Wisconsin.
Participants by arm
| Arm | Count |
|---|---|
| Panobinostat Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Panobinostat |
|---|---|
| Age, Customized 40-49 years of age | 3 participants |
| Age, Customized 50-59 years of age | 5 participants |
| Age, Customized 60-69 years of age | 4 participants |
| Age, Customized 70-79 years of age | 2 participants |
| Age, Customized >= 80 years of age | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 6 / 15 |
Outcome results
Primary
Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Confirmed anti-tumor response rate will be validated by the Response Evaluation Criteria in Solid Tumors (RECIST). All participants included in the study will be assessed for response to the proposed panobinostat treatment, even if there are protocol treatment deviations. Each participant will be assigned one of the following categories: complete response, partial response, stable disease, progressive disease, early death from malignant disease, early death from toxicity, early death because of other cause, or unknown.
Time frame: every 8 weeks, up to 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Stable Disease | 15 participants |
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Complete Response | 0 participants |
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Partial Response | 0 participants |
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Progressive Disease | 0 participants |
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Early death from malignant disease | 0 participants |
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Early death from toxicity | 0 participants |
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Early death because of other cause | 0 participants |
| Panobinostat | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Unknown | 0 participants |
Secondary
Delineate the Expression of Notch 1 in Neuroendocrine Tumor Samples Before and During Treatment With Panobinostat
The expression of Notch 1 in neuroendocrine tumor samples will be evaluated prior to Cycle 1 Day 1 dose and at the end of Cycle 2 of treatment of treatment.
Time frame: Pre-treatment and up to week 12
Population: Data to delineate the expression of Notch 1 in neuroendocrine tumor samples was not collected. The question regarding the role of Notch1 in well-differentiated NET remains unanswered.
Secondary
Evaluate the Overall Survival of Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panobinostat | Evaluate the Overall Survival of Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat | 47.27 months |
Secondary
Evaluate the Time to Progression for Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Panobinostat | Evaluate the Time to Progression for Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat | 9.9 months |
Secondary
Number of Participants With Toxicities
Evaluate the toxicity and tolerability of panobinostat in the patient population
Time frame: up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panobinostat | Number of Participants With Toxicities | 5 participants |