Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Anti-Infective Agents

Everolimus

Liver Extracts

Pasireotide

Somatostatin

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Hormones

Hormone Antagonists

Oral Everolimus 7.5 mg administered daily for 28 days per cycle, plus pasireotide Long Acting Release (LAR) 60 mg administered by intramuscular injection once per 28 day cycle on day 1.

Everolimus 7.5 mg administered daily for 28 days per cycle until disease progression or unacceptable toxicity.

Monthly (every 28 days) intramuscular injection of long-acting pasireotide (pasireotide LAR 60 mg) repeated on day 1 of every 28 day cycle until disease progression or unacceptable toxicity.

Hanna Sanoff, MD

The purpose of this study is to estimate the time to disease progression when everolimus and pasireotide are given together in patients with advanced or metastatic HCC who have not had any prior systemic therapy.

This open label, single-arm Phase II study will assess time to progression (TTP) and safety of everolimus and pasireotide in patients with advanced or metastatic hepatocellular carcinoma (HCC) and limited prior systemic therapy. Should this regimen demonstrate efficacy, this will support a Phase III randomized clinical trial of this combination therapy. At least 30 patients will be enrolled into this Phase II study. Additionally, given the potential importance of the RAS/RAF/MEK/ERK and RAS/pAKT pathways, we propose to correlate outcomes with baseline pAKT, p-S6, somatostatin receptor tumor expression, and serum VEGF expression. We anticipate these exploratory analyses will increase understanding of the molecular pathways and their inhibition in this disease. The study will be performed as a University of North Carolina-coordinated, multicenter study.

Everolimus and Pasireotide (SOM230) in Patients With Advanced or Metastatic Hepatocellular Carcinoma

Phase II Single Arm Study of Everolimus and Pasireotide (SOM230) in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC)

Time to progression is defined as the time from study enrollment until radiological progression in a previously embolized lobe, development of new lesions in an untreated lobe, or evidence of extrahepatic progression (based on modified Hepatocellular Carcinoma (HCC) Response Evaluation Criteria In Solid Tumors (RECIST) criteria). Patients will be followed until death. Patients that die of causes unrelated to the study drug without evidence of progression will be censored.

Safety determinations are based on the rate of drug-related adverse events (AEs) reported based upon the toxicity as measured by the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

Overall survival is defined as the time from study enrollment until death.

ORR is the rate of complete responses (CRs) + partial responses (PRs) as determined by RECIST (v1.1) and modified HCC RECIST criteria. Responses defined as follows:

CR: disappearance of all clinical/radiological evidence of tumor including any intratumoral arterial enhancement in all target lesions.

Partial Response (PR): at least a 30% decrease in the sum of diameters of viable (contrast enhancement in the arterial phase) target lesions, referencing the baseline sum.

Stable Disease (SD): any cases that do not qualify for either partial response or progressive disease.

Progressive Disease (PD): an increase of at least 20% in the sum of the diameters of viable target lesions, referencing the nadir sum, and/or the appearance of one or more new lesions. A new hepatic nodule signals PD when the longest diameter is at least 10 mm and the nodule shows the typical vascular pattern of HCC on dynamic imaging or if at least 1-cm interval growth is seen in subsequent scans.

Novartis Pharmaceuticals

UNC Lineberger Comprehensive Cancer Center

Oral Everolimus 7.5 mg administered daily for 28 days per cycle, plus pasireotide LAR 60 mg administered by intramuscular injection once per 28 day cycle on day 1.

Everolimus: Everolimus 7.5 mg administered daily for 28 days per cycle until disease progression or unacceptable toxicity.

Pasireotide: Monthly (every 28 days) intramuscular injection of long-acting pasireotide (pasireotide LAR 60 mg) repeated on day 1 of every 28 day cycle until disease progression or unacceptable toxicity.

Everolimus + Pasireotide

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Present

Absent

Presence of Hepatitis C virus as a cause of hepatocellular carcinoma

Chronic Hepatitis C

Presence of Hepatitis B virus as a cause of hepatocellular carcinoma

Chronic Hepatitis B

A scale to assess severity of liver disease based on five clinical features: 1) serum bilirubin, 2) serum albumin, 3) prothrombin time, 4) the degree of ascites, and 5) the grade of hepatic encephalopathy. One point given for absent/normal, 2 points for slight or mild, and 3 points for severe. Child-Pugh Score could range from 5 - 15, with lower scores equaling better prognosis.

Child-Pugh Score (Stage)

Time from diagnosis to enrollment

The CLIP score for a patient with hepatocellular carcinoma is calculated by assigning a score (0, 1 or 2) to each of four clinical factors: a) Child-Pugh stage; b) number of tumor nodules and whether the tumor extends through \<=50% or \>50% of the liver; c) AFP; and d) portal vein thrombosis.

These scores are added together to yield a CLIP score of 0-6, with lower scores having a better outcome.

CLIP (Cancer of the Liver Italian Program) score

Stage B

Stage C

Missing

Missing for one participant. Barcelona Clinic Liver Cancer (BCLC) staging criteria ranges from very early stage (0), to early stage (A), Intermediate stage (B), advanced stage (C), and end stage (D). Staging is based on Child-Pugh score, performance status, and number and size of nodules. Earlier stages (0,A) have better prognosis.

BCLC (Barcelona Clinic Liver Cancer) Stage

Portal vein involvement

Unifocal

Multifocal

Metastatic

Extent of cancer

Transarterial chemoembolization (TACE)

Transarterial radioembolization (TARE)

Ablation

Surgery

None

Participants may have received more than one type of prior therapy.

Prior therapy received for this cancer

Unplanned interim analysis due to negative results from another trial found conditional probability of rejecting null hypothesis based on events in the 24 patients enrolled was 0.08. Accrual goals had been met and study was complete per protocol.

Dr. Hanna Sanoff

Time to Progression (TTP)

Dose Limiting Toxicities (DLT)

Any adverse event

Number of Individuals Experiencing Toxicity

Overall Survival (OS)

Radiographic response (CR or PR)

Stable disease

Two patients were not evaluable; one due to death prior to radiographic evaluation (death clinically attributed to progressive disease) and the other due to early termination of treatment due to intolerance.

Objective Response Rate (ORR)

Overall Study

Spots Global Cancer Trial Database for Everolimus and Pasireotide (SOM230) in Patients With Advanced or Metastatic Hepatocellular Carcinoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial