Pasireotide, Everolimus and Selective Internal Radioembolization Therapy for Unresectable Hepatic Metastases
This trial is active, not recruiting.
|Treatments||pasireotide, sir-sphere radioembolization, everolimus|
|Start date||December 2011|
|End date||December 2016|
|Trial size||13 participants|
|Trial identifier||NCT01469572, IRB00051599, WCI2031-11|
The purpose of this study is to see the safety and activity of using pasireotide, everolimus and radioembolization (Selective Internal Radioembolization Therapy-SIRT) in the treatment of neuroendocrine tumors (carcinoid) that has spread to the liver. Both everolimus or radioembolization are considered "standard of care" regimens in patients with liver lesions from neuroendocrine tumors. However, the use of the combination of everolimus and radioembolization has not been formally evaluated in the setting of a clinical trial. Pasireotide is a medication that is intended to block the hormonal secretions from the neuroendocrine tumors.
This study is divided into two parts. In the first part, the aim of the study is to determine the safety of combining everolimus, pasireotide, and radioembolization. For this part of the study the investigators will enroll up to 18 patients. After the investigators confirm the safety of the combination, they will conduct the second part of the study which will focus on evaluating the effectiveness of the combination. For this part of the study the investigators intend to enroll a total of 37 patients.
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
Evaluate the number of patients who develop side effects from combination therapy.
time frame: 1 month
Compare the size of the tumor before and three months after treatment using cross sectional imaging (CT ro MRI)
time frame: 3 months
Male or female participants at least 18 years old.
Inclusion Criteria: 1. Confirmed low to intermediate grade neuroendocrine tumors with unresectable liver metastasis 2. Patients must have evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) despite optimal octreotide therapy (octreotide LAR 30 mg every month) 3. Prior treatment permitted include: surgery, prior systemic therapies (less than 2 prior lines of chemotherapy), or radiation therapy 4. Patients must have measurable disease by RECIST 1.1 criteria 5. For the patients in the phase Ib study, neuroendocrine tumor must involve both liver lobes 6. Minimum of four weeks since any major surgery, completion of radiation, or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy) 7. Age greater than 18 years 8. Adequate bone marrow function as shown by: absolute neutrophil count (ANC) greater than or equal to 1.5 x 109 L, platelets greater than or equal to 100 x 109/L, Hb greater than9 g dL 9. Adequate liver function as shown by: - serum bilirubin less than or equal to 1.5 x upper limit of normal (ULN) - alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5x ULN (less than or equal to 5x ULN in patients with liver metastases) - international normalized ratio (INR) less than or equal to 1.5. (Anticoagulation is allowed if target INR less than or equal to 1.5 on a stable dose of warfarin or on a stable dose of low molecular weight (LMW) heparin for grater than 2 weeks at time of randomization.) 10. Adequate renal function: serum creatinine less than or equal to 1.5 x ULN Exclusion Criteria: 1. Contraindications to angiography 2. Patients with extensive tumor replacement of the liver defined as tumor volume greater than 50 percent of liver 3. Prior treatment with any investigational drug within the preceding 4 weeks 4. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases 5. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: - Symptomatic congestive heart failure of New York Heart Association Class III or IV - unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease - severely impaired lung function as defined as spirometry and diffusing capacity of lung for carbon monoxide (DLCO) that is 50 percent of the normal predicted value and/or 02 saturation that is 88 percent or less at rest on room air - uncontrolled diabetes as defined by hemoglobin A1C (HbA1c) greater than 7 percent despite therapy - active (acute or chronic) or uncontrolled severe infections - liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C) 6. A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection. 7. Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot) 8. Patients with an active, bleeding diathesis 9. Patients who have received prior treatment with a mammalian target of rapamycin (mTOR) inhibitor (e.g., sirolimus, temsirolimus, everolimus) 10. Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR formulations
|Official title||Phase IB/II Study of Pasireotide, Everolimus and Selective Internal Radioembolization Therapy (SIRT) for Unresectable Neuroendocrine Hepatic Metastases|
|Principal investigator||Bassel El-Rayes, MD|
|Description||Liver metastasis remain a major challenge in the care of patients with Neuroendocrine Tumors (NET). This study is evaluating the combination of systemic therapies plus radioembolization for the treatment of liver metastasis from NET. The study allows pancreatic and intestinal NET that have spread to the liver.|
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