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

NCT01469572 | Completed Phase 1 DMC

• 2 other identifiers: IRB00051599WCI2031-11
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuroendocrine Tumors

Keywords

Neuroendocrine hepatic tumors; Liver cancer; Metastatic liver cancer

Outcome Measures

Primary Outcomes (1)

• Evaluate the number of patients who develop side effects from combination therapy.

  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.

  1 month

Secondary Outcomes (1)

• Compare the size of the tumor before and three months after treatment using cross sectional imaging (CT ro MRI)

  3 months

Study Arms (1)

Sir-sphere radioembolization

EXPERIMENTAL

Everolimus, Pasireotide and Sir-sphere radioembolization

Drug: Pasireotide; Procedure: Sir-sphere Radioembolization; Drug: Everolimus

Interventions

Pasireotide DRUG

Pasireotide is given as an injection.

Also known as: SOM230, Signifor

Sir-sphere radioembolization

Sir-sphere Radioembolization PROCEDURE

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.

Also known as: Selective Internal Radioembolization Therapy, SIRT

Sir-sphere radioembolization

Everolimus DRUG

Given orally every day for the duration of the study

Also known as: RAD001, Afinitor

Sir-sphere radioembolization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed low to intermediate grade neuroendocrine tumors with unresectable liver metastasis
• Patients must have evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) despite optimal octreotide therapy (octreotide long acting release \[LAR\] 30 mg every month)
• Prior treatment permitted include: surgery, prior systemic therapies (≤ 2 prior lines of chemotherapy), or radiation therapy
• Patients must have measurable disease by RECIST 1.1 criteria
• For the patients in the phase Ib study, neuroendocrine tumor must involve both liver lobes
• 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)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Adequate bone marrow function as shown by:
• Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10\^9/L
• Platelets greater than or equal to 100 x 10\^9/L
• Hb greater than 9 g/dL
• Adequate liver function as shown by:
• Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x ULN (≤ 3x ULN in patients with liver metastases)
• International normalized ratio (INR) ≤ 1.5 (anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin)

You may not qualify if:

• Evidence of ascites, cirrhosis, portal hypertension or portal vein thrombosis
• Prior radiation to the upper abdomen
• Contraindications to angiography
• Patients with extensive tumor replacement of the liver defined as tumor volume \> 50% of liver
• Lung shunt ≥ 20%
• Prior treatment with any investigational drug within the preceding 4 weeks
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
• 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% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
• Uncontrolled diabetes as defined by hemoglobin A1C (HbA1c) \> 7% despite therapy.

Sponsors & Collaborators

• Emory University: lead
• Novartis: collaborator

Study Sites (1)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Kim HS, Shaib WL, Zhang C, Nagaraju GP, Wu C, Alese OB, Chen Z, Brutcher E, Renfroe M, El-Rayes BF. Phase 1b study of pasireotide, everolimus, and selective internal radioembolization therapy for unresectable neuroendocrine tumors with hepatic metastases. Cancer. 2018 May 1;124(9):1992-2000. doi: 10.1002/cncr.31192. Epub 2018 Feb 16.

  PMID: 29451701 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors; Liver Neoplasms

Interventions

pasireotide; Sirtuins; Everolimus

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Group III Histone Deacetylases; Histone Deacetylases; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; ADP Ribose Transferases; Pentosyltransferases; Glycosyltransferases; Transferases; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Bassel El-Rayes, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 13, 2011
• First Posted: November 10, 2011
• Study Start: December 1, 2011
• Primary Completion: October 1, 2018
• Study Completion: October 1, 2018
• Last Updated: October 18, 2018

Record last verified: 2018-10

Locations

US (1)