Study of Pasireotide Long Acting Release (LAR) in Patients With Metastatic Neuroendocrine Tumors (NETs)

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01253161
• Collaborator: Novartis Pharmaceuticals (Industry), RECORDATI GROUP (Industry)
• Enrollment: 29
• Locations: 2
• Arm: 1
• Anticipated Duration (Months): 142
• Patients Per Site: 14.5
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Neuroendocrine Tumors; Carcinoid Tumors	Drug: Pasireotide Long Acting Release (LAR)	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Pasireotide LAR in Patients With Metastatic Neuroendocrine Carcinomas
• Actual Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Oct 6, 2021
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pasireotide LAR Treatment The investigational drug used in this study is pasireotide long acting release (LAR) 60 mg.	Drug: 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.; Other Names: SOM 230

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Institute	Stanford	California	United States	94305
2	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Novartis Pharmaceuticals
• RECORDATI GROUP

Investigators

• Principal Investigator: Jonathan Strosberg, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 11, 2020

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01253161
• Other Study ID Numbers: MCC-16438; CSOM230DUS23T
• First Posted: Dec 3, 2010
• Last Update Posted: Apr 19, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: advanced; metastatic; unresectable; carcinoma; gastrointestinal tract; lungs; colon; liver; rectum; small intestine; stomach; pancreatic
• Additional relevant MeSH terms: Neoplasms; Neuroendocrine Tumors; Carcinoid Tumor; Pasireotide

Study Results

Participant Flow

Arm/Group Title	Pasireotide LAR Treatment
Arm/Group Description	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.
Period Title: Overall Study
STARTED	29
COMPLETED	28
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Pasireotide LAR Treatment
Arm/Group Description	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.
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	22 75.9%
>=65 years	7 24.1%
Sex: Female, Male (Count of Participants)
Female	10 34.5%
Male	19 65.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 10.3%
Not Hispanic or Latino	25 86.2%
Unknown or Not Reported	1 3.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 10.3%
White	23 79.3%
More than one race	0 0%
Unknown or Not Reported	2 6.9%
Region of Enrollment (participants) [Number]
United States	29 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Evaluable participants

Arm/Group Title	Pasireotide LAR Treatment
Arm/Group Description	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.
Measure Participants	28
Median (95% Confidence Interval) [months]	11

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

evaluable participants

Arm/Group Title	Pasireotide LAR Treatment
Arm/Group Description	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.
Measure Participants	28
Partial Response	4 13.8%
Stable Disease	60 206.9%
Progressive Disease	36 124.1%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug

Arm/Group Title	Pasireotide LAR Treatment
Arm/Group Description	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.
Measure Participants	29
Number [events]	42

Adverse Events

Time Frame	Adverse events collected for 28 days after last dose of study drug, up to 60 months.
Arm/Group Title	Pasireotide LAR Treatment
Arm/Group Description	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.
All Cause Mortality
	Pasireotide LAR Treatment
	Affected / at Risk (%)	# Events
Total	6/29 (20.7%)
Serious Adverse Events
	Pasireotide LAR Treatment
	Affected / at Risk (%)	# Events
Total	12/29 (41.4%)
Cardiac disorders
Cardiac Disorders - Other	1/29 (3.4%)	1
Sinus tachycardia	1/29 (3.4%)	1
Gastrointestinal disorders
Dueodenal obstruction	1/29 (3.4%)	1
Gastrointestinal disorders - Other	1/29 (3.4%)	1
Nausea	2/29 (6.9%)	2
Anorexia	1/29 (3.4%)	1
Abdominal pain	2/29 (6.9%)	2
Colonic perforation	1/29 (3.4%)	1
Vomiting	1/29 (3.4%)	1
Ileal obstruction	1/29 (3.4%)	2
Infections and infestations
Kidney infection	1/29 (3.4%)	1
Skin infection	1/29 (3.4%)	1
Lung infection	1/29 (3.4%)	1
Bladder infection	1/29 (3.4%)	1
Investigations
Platelet count decreased	1/29 (3.4%)	1
Creatinine increased	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	Pasireotide LAR Treatment
	Affected / at Risk (%)	# Events
Total	28/29 (96.6%)
Blood and lymphatic system disorders
Anemia	2/29 (6.9%)	6
Cardiac disorders
Cardiac disorders - Other	2/29 (6.9%)	3
Eye disorders
Blurred vision	2/29 (6.9%)	2
Eye disorders - Other	1/29 (3.4%)	1
Gastrointestinal disorders
Diarrhea	11/29 (37.9%)	13
Abdominal pain	9/29 (31%)	17
Constipation	6/29 (20.7%)	7
Nausea	5/29 (17.2%)	6
Vomiting	5/29 (17.2%)	6
Gastrointestinal disorders - Other	4/29 (13.8%)	4
Bloating	2/29 (6.9%)	5
Dyspepsia	1/29 (3.4%)	1
Flatulence	1/29 (3.4%)	2
Gastritis	1/29 (3.4%)	1
Malabsorption	1/29 (3.4%)	1
Mucositis oral	1/29 (3.4%)	1
Small intestinal obstruction	1/29 (3.4%)	1
General disorders
Fatigue	12/29 (41.4%)	19
Edema limbs	4/29 (13.8%)	4
Pain	3/29 (10.3%)	3
Chills	2/29 (6.9%)	2
Fever	2/29 (6.9%)	2
Non-cardiac chest pain	1/29 (3.4%)	1
Pain in extremity	2/29 (6.9%)	2
Hepatobiliary disorders
Cholecystitis	1/29 (3.4%)	1
Infections and infestations
Bladder infection	1/29 (3.4%)	1
Bronchial infection	1/29 (3.4%)	1
Infections and infestations - Other	1/29 (3.4%)	1
Skin infection	1/29 (3.4%)	1
Urinary tract infection	1/29 (3.4%)	1
Injury, poisoning and procedural complications
Bruising	1/29 (3.4%)	1
Investigations
Alkaline phosphatase increased	3/29 (10.3%)	4
Alanine aminotransferase increased	2/29 (6.9%)	8
Aspartate aminotransferase increased	2/29 (6.9%)	2
Creatinine increased	2/29 (6.9%)	5
Weight loss	2/29 (6.9%)	3
Blood bilirubin increased	1/29 (3.4%)	1
Investigations - Other	1/29 (3.4%)	1
Pancreatic enzymes decreased	1/29 (3.4%)	1
Platelet count decreased	1/29 (3.4%)	3
Weight gain	1/29 (3.4%)	2
Metabolism and nutrition disorders
Hyperglycemia	24/29 (82.8%)	147
Anorexia	4/29 (13.8%)	5
Hyperkalemia	2/29 (6.9%)	14
Hyponatremia	2/29 (6.9%)	12
Dehydration	1/29 (3.4%)	1
Glucose intolerance	1/29 (3.4%)	1
Hypercalcemia	1/29 (3.4%)	5
Hypermagnesemia	1/29 (3.4%)	1
Hypokalemia	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	4/29 (13.8%)	6
Myalgia	3/29 (10.3%)	3
Bone pain	2/29 (6.9%)	2
Arthralgia	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorder - Other	1/29 (3.4%)	1
Neck pain	1/29 (3.4%)	1
Nervous system disorders
Headache	5/29 (17.2%)	7
Dizziness	4/29 (13.8%)	4
Dysgeusia	1/29 (3.4%)	1
Nervous system disorders - Other	1/29 (3.4%)	1
Peripheral sensory neuropathy	1/29 (3.4%)	1
Psychiatric disorders
Depression	2/29 (6.9%)	3
Anxiety	1/29 (3.4%)	1
Insomnia	1/29 (3.4%)	1
Renal and urinary disorders
Renal and urinary disorders - Other	1/29 (3.4%)	2
Urinary frequency	1/29 (3.4%)	1
Reproductive system and breast disorders
Breast pain	1/29 (3.4%)	1
Vaginal discharge	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	5/29 (17.2%)	5
Cough	2/29 (6.9%)	2
Respiratory, thoracic and mediastinal disorders - Other	2/29 (6.9%)	2
Hoarseness	1/29 (3.4%)	1
Productive cough	1/29 (3.4%)	1
Sneezing	1/29 (3.4%)	1
Wheezing	1/29 (3.4%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	3/29 (10.3%)	3
Skin and subcutaneous tissue disorders - Other	2/29 (6.9%)	2
Dry skin	1/29 (3.4%)	1
Pruritus	1/29 (3.4%)	1
Vascular disorders
Hypertension	8/29 (27.6%)	30
Flushing	1/29 (3.4%)	1
Hot flashes	1/29 (3.4%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.