Study of Pasireotide Long Acting Release (LAR) in Patients With Metastatic Neuroendocrine Tumors (NETs)
Primary Purpose
Neuroendocrine Tumors, Carcinoid Tumors
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pasireotide Long Acting Release (LAR)
Sponsored by
About this trial
This is an interventional treatment trial for Neuroendocrine Tumors focused on measuring advanced, metastatic, unresectable, carcinoma, gastrointestinal tract, lungs, colon, liver, rectum, small intestine, stomach, pancreatic
Eligibility Criteria
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
Sites / Locations
- Stanford Cancer Institute
- H. Lee Moffitt Cancer Center and Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pasireotide LAR Treatment
Arm Description
The investigational drug used in this study is pasireotide long acting release (LAR) 60 mg.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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).
Full Information
NCT ID
NCT01253161
First Posted
November 30, 2010
Last Updated
March 2, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Novartis Pharmaceuticals, RECORDATI GROUP
1. Study Identification
Unique Protocol Identification Number
NCT01253161
Brief Title
Study of Pasireotide Long Acting Release (LAR) in Patients With Metastatic Neuroendocrine Tumors (NETs)
Official Title
Phase II Study of Pasireotide LAR in Patients With Metastatic Neuroendocrine Carcinomas
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
February 1, 2011 (Actual)
Primary Completion Date
October 6, 2021 (Actual)
Study Completion Date
March 2, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Novartis Pharmaceuticals, RECORDATI GROUP
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Tumors, Carcinoid Tumors
Keywords
advanced, metastatic, unresectable, carcinoma, gastrointestinal tract, lungs, colon, liver, rectum, small intestine, stomach, pancreatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
29 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pasireotide LAR Treatment
Arm Type
Experimental
Arm Description
The investigational drug used in this study is pasireotide long acting release (LAR) 60 mg.
Intervention Type
Drug
Intervention Name(s)
Pasireotide Long Acting Release (LAR)
Other Intervention Name(s)
SOM 230
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS) at One Year
Description
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
Secondary Outcome Measure Information:
Title
Overall Radiographic Response Rate (ORR)
Description
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
Title
Adverse Events Possibly Related to Study Treatment
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Strosberg, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Cancer Institute
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25376618
Citation
Cives M, Kunz PL, Morse B, Coppola D, Schell MJ, Campos T, Nguyen PT, Nandoskar P, Khandelwal V, Strosberg JR. Phase II clinical trial of pasireotide long-acting repeatable in patients with metastatic neuroendocrine tumors. Endocr Relat Cancer. 2015 Feb;22(1):1-9. doi: 10.1530/ERC-14-0360. Epub 2014 Nov 6.
Results Reference
derived
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Study of Pasireotide Long Acting Release (LAR) in Patients With Metastatic Neuroendocrine Tumors (NETs)
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