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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01253161
First received: November 30, 2010
Last updated: May 6, 2016
Last verified: May 2016
  Purpose
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 Intervention Phase
Neuroendocrine Tumors
Carcinoid Tumors
Drug: Pasireotide Long Acting Release (LAR)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Pasireotide LAR in Patients With Metastatic Neuroendocrine Carcinomas

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Rate of Progression-free Survival (PFS) at One Year [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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:
  • Median Overall Survival (OS) [ Time Frame: Up to 48 months ] [ Designated as safety issue: No ]
    OS: The date of first study treatment to the date of death due to any cause.

  • Overall Radiographic Response Rate (ORR) [ Time Frame: Up to 48 months ] [ Designated as safety issue: No ]
    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.

  • Occurrence of Adverse Events Possibly Related to Study Treatment [ Time Frame: Up to 48 months ] [ Designated as safety issue: Yes ]
    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).


Enrollment: 29
Study Start Date: January 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment phase Drug: Pasireotide Long Acting Release (LAR)
Intramuscular injection of Pasireotide LAR
Other Name: SOM 230

Detailed Description:

This is a multi-institutional, prospective phase II open-label trial.

The investigational drug used in this study is pasireotide LAR 60mg. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 Tosades 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01253161

Locations
United States, California
Stanford Cancer Institute
Stanford, California, United States, 94305
United States, Florida
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
Investigators
Principal Investigator: Jonathan Strosberg, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01253161     History of Changes
Other Study ID Numbers: MCC-16438  CSOM230DUS23T 
Study First Received: November 30, 2010
Last Updated: May 6, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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:
Neuroendocrine Tumors
Carcinoid Tumor
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on August 28, 2016