Carcinoid Tumors, Neuroendocrine Tumors
Conditions
Keywords
advanced, metastatic, unresectable, carcinoma, gastrointestinal tract, lungs, colon, liver, rectum, small intestine, stomach, pancreatic
Brief summary
The goal of this clinical research study is to learn if the study drug, Pasireotide LAR can shrink or slow the growth of Metastatic Neuroendocrine Carcinomas. The safety of this drug will also be studied. The patient's physical state, changes in the size of the tumor, and laboratory findings taken while on-study will help us decide if Pasireotide LAR is safe and effective.
Detailed description
This is a multi-institutional, prospective phase II open-label trial. The investigational drug used in this study is pasireotide LAR 60 mg. Pasireotide will be administered as an intramuscular injection at the beginning of every cycle which is defined as 28 days (+/- 3 days). Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent. Safety and efficacy will be assessed throughout the treatment period.
Interventions
DRUGPasireotide Long Acting Release (LAR)
Pasireotide will be administered as an intramuscular injection at the beginning of every cycle which is defined as 28 days (+/- 3 days). Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent.
Sponsors
Novartis Pharmaceuticals
RECORDATI GROUP
H. Lee Moffitt Cancer Center and Research Institute
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
* Locally unresectable or metastatic carcinoid or pancreatic neuroendocrine tumors * Tumors must be considered well or moderately differentiated (or low to intermediate grade). Patients with poorly differentiated neuroendocrine carcinomas or small cell carcinomas are excluded from the study. * No prior systemic antineoplastic neuroendocrine tumor treatment (including prior somatostatin analogs). However patients who have received a short course of subcutaneous (SQ) octreotide (\<10 days) in the past are eligible if \> 1 week has elapsed from their last octreotide injection. * Minimum of four weeks since any major surgery * Measureable disease by Response Evaluation Criteria in Solid Tumors (RECIST) * Eastern Cooperative Oncology Group (ECOG) performance status ≤1 * Life expectancy 12 weeks or more * Adequate bone marrow function as shown by: absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L, Platelets ≥ 75 x 10\^9/L, hemoglobin (Hgb) \> 8 g/dL * Adequate liver function as shown by: serum bilirubin ≤ 2.0 x upper limit of normal (ULN), and serum transaminases activity ≤ 2 x ULN, with the exception of serum transaminases (\< 3 x ULN) if the patient has liver metastases * Adequate renal function as shown by serum creatinine ≤ 2.0 x ULN * Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. * Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating. Both men and WOCBP must be advised of the importance of using effective birth control measures during the course of the study. * Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks by the investigator (or his/her designee) with the aid of written information.
Exclusion criteria
* Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases * Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for 5 years * Patients with uncontrolled diabetes mellitus or a fasting plasma glucose \> 1.5 ULN or glycosylated hemoglobin (HbA1c) \>8%. Note: At the principle investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted. * Patients with symptomatic cholelithiasis * Patients who have congestive heart failure: New York Heart Association (NYHA) Class III or IV, unstable angina, or a history of acute myocardial infarction within the 6 months preceding enrollment * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * Severely impaired lung function * Any active (acute or chronic) or uncontrolled infection/ disorders * Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy * Known hypersensitivity to somatostatin analogues or any component of the pasireotide LAR formulation * Corrected QT interval (QTcF) of \>470 msec on screening Electrocardiogram (ECG) * Risk factors for Torsades de Pointes such as cardiac failure, clinically significant/symptomatic bradycardia * Clinically significant hypokalemia or hypomagnesemia that are not correctable * History of sustained ventricular tachycardia, ventricular fibrillation, advanced heart block, or idiopathic syncope thought to be related to ventricular arrhythmia * Concomitant medication(s) known to increase the QT interval * History of noncompliance to medical regimens or unwillingness to comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) at One Year | 12 months | PFS: Defined as the time from the date of first study treatment to the date of the first documented disease progression, by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) guidelines, or death due to any cause. Progressive Disease (PD): at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Radiographic Response Rate (ORR) | Up to 48 months | Complete response (CR): complete disappearance of all target lesions, confirmed by repeat assessments at no less than 4 weeks after the criteria for response are first met. Partial response (PR): at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. This must be confirmed by repeat assessment at no less than 4 weeks after the criteria for response are first met. Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. |
| Adverse Events Possibly Related to Study Treatment | Up to 48 months | Adverse Events (AEs) and Serious Adverse Events (SAEs) will be evaluated continuously throughout the study. Safety and tolerability will be assessed according to the NIH/NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pasireotide LAR Treatment The investigational drug used in this study is pasireotide long acting release (LAR) 60 mg.
Pasireotide Long Acting Release (LAR): Pasireotide will be administered as an intramuscular injection at the beginning of every cycle which is defined as 28 days (+/- 3 days). Study treatment should begin within 14 days following enrollment into the study and continue until disease progression, unacceptable toxicity, or withdrawal of consent. | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Pasireotide LAR Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 2 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 29 |
| other Total, other adverse events | 28 / 29 |
| serious Total, serious adverse events | 12 / 29 |
Outcome results
Primary
Progression-free Survival (PFS) at One Year
PFS: Defined as the time from the date of first study treatment to the date of the first documented disease progression, by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) guidelines, or death due to any cause. Progressive Disease (PD): at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Time frame: 12 months
Population: Evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pasireotide LAR Treatment | Progression-free Survival (PFS) at One Year | 11 months |
Secondary
Adverse Events Possibly Related to Study Treatment
Adverse Events (AEs) and Serious Adverse Events (SAEs) will be evaluated continuously throughout the study. Safety and tolerability will be assessed according to the NIH/NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Time frame: Up to 48 months
Population: All participants who received at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pasireotide LAR Treatment | Adverse Events Possibly Related to Study Treatment | 42 events |
Secondary
Overall Radiographic Response Rate (ORR)
Complete response (CR): complete disappearance of all target lesions, confirmed by repeat assessments at no less than 4 weeks after the criteria for response are first met. Partial response (PR): at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. This must be confirmed by repeat assessment at no less than 4 weeks after the criteria for response are first met. Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.
Time frame: Up to 48 months
Population: evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pasireotide LAR Treatment | Overall Radiographic Response Rate (ORR) | Partial Response | 4 percentage of participants |
| Pasireotide LAR Treatment | Overall Radiographic Response Rate (ORR) | Stable Disease | 60 percentage of participants |
| Pasireotide LAR Treatment | Overall Radiographic Response Rate (ORR) | Progressive Disease | 36 percentage of participants |