Pasireotide, Everolimus and Selective Internal Radioemboilization Therapy for Unresectable Hepatic Metastases

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Bassel El-Rayes, Emory University
ClinicalTrials.gov Identifier:
NCT01469572
First received: October 13, 2011
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Neuroendocrine Tumors
Drug: Pasireotide
Procedure: Sir-sphere Radioembolization
Drug: Everolimus
Phase 1
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: WCI2031-11: Phase IB/II Study of Pasireotide, Everolimus and Selective Internal Radioemboilization Therapy (SIRT) for Unresectable Neuroendocrine Hepatic Metastases

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Evaluate the number of patients who develop side effects from combination therapy. [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
    Determine the maximum tolerated dose of pasireotide and everolimus that can be administered with SIR Spheres. Patients will be treated in cohorts of three. Dose of everolimus will be increased after every three patients. Plan is to determine the maximum dose that can be administered with less than 2 out of 6 patients develop significant side effects.


Secondary Outcome Measures:
  • Compare the size of the tumor before and three months after treatment using cross sectional imaging (CT ro MRI) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    To evaluate the response rate associated with the combination of pasireotide, everolimus and radioembolization. Response is defined as radiologic shrinkage in the size of the tumor.


Estimated Enrollment: 49
Study Start Date: December 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sir-sphere radioembolization
Everolimus, Pasireotide and Sir-sphere radioembolization
Drug: Pasireotide
Pasireotide is given as an injection.
Other Name: Pasireotide other names are SOM230
Procedure: Sir-sphere Radioembolization
A catheter will be placed in a branch of the hepatic artery (Liver) that supplies the tumor with blood. Radioactive beads will be injected into the tumor through the catheter.
Other Name: Sir-sphere Radioembolization
Drug: Everolimus
Given orally every day for the duration of the study
Other Name: Everolimus, RAD001

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed low to intermediate grade neuroendocrine tumors with unresectable liver metastasis
  2. Patients must have evidence of disease progression by 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 RESICT 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: 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 ULN
    • ALT and AST less than or equal to 2.5x ULN (less than or equal to 5x ULN in patients with liver metastases)
    • 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 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 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. HBV DNA and HCV RNA 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. See section 3.2.5.1 for the detailed management and monitoring of patients with HBV/HCV infection on trial.
  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 an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus).
  10. Known hypersensitivity to somatostatin analogues or any component of the pasireotide or octreotide LAR formulations
  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: NCT01469572

Contacts
Contact: Bassel El-Rayes, MD 1-888-946-7447 bassel.el-rayes@emoryhealthcare.org

Locations
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30303
Sponsors and Collaborators
Emory University
Novartis
Investigators
Principal Investigator: Bassel El-Rayes, MD Emory University Winship Cancer Institute
Principal Investigator: Hyun S Kim, MD, Co-PI Emory University
  More Information

No publications provided

Responsible Party: Bassel El-Rayes, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01469572     History of Changes
Other Study ID Numbers: IRB00051599, WCI2031-11
Study First Received: October 13, 2011
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
Neuroendocrine hepatic tumors
Liver cancer
Metastatic liver cancer

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on September 16, 2014