Trial Outcomes & Findings for Everolimus and Pasireotide (SOM230) in Patients With Advanced or Metastatic Hepatocellular Carcinoma (NCT NCT01488487)

Last Updated: 2016-04-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

3.5 years

Results posted on

2016-04-07

Participant Flow

Of the 33 participants screened for eligibility, 24 were deemed eligible and went on to treatment, 8 were ineligible, and 1 participant withdrew consent prior to treatment assignment.

Participant milestones

Participant milestones
Measure	Everolimus + Pasireotide 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.
Overall Study STARTED	24
Overall Study Received Treatment	24
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus + Pasireotide 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.
Overall Study Adverse Event	6
Overall Study Death	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus + Pasireotide n=24 Participants 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.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=99 Participants
Age, Categorical >=65 years	9 Participants n=99 Participants
Age, Continuous	59 years n=99 Participants
Sex: Female, Male Female	8 Participants n=99 Participants
Sex: Female, Male Male	16 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants
Race (NIH/OMB) White	21 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	24 participants n=99 Participants
Chronic Hepatitis C Present	7 participants n=99 Participants
Chronic Hepatitis C Absent	17 participants n=99 Participants
Chronic Hepatitis B Present	2 participants n=99 Participants
Chronic Hepatitis B Absent	22 participants n=99 Participants
Child-Pugh Score (Stage)	5 units on a scale n=99 Participants
Time from diagnosis to enrollment	4 Months n=99 Participants
CLIP (Cancer of the Liver Italian Program) score	1.5 units on a scale n=99 Participants
BCLC (Barcelona Clinic Liver Cancer) Stage Stage B	2 participants n=99 Participants
BCLC (Barcelona Clinic Liver Cancer) Stage Stage C	21 participants n=99 Participants
BCLC (Barcelona Clinic Liver Cancer) Stage Missing	1 participants n=99 Participants
Portal vein involvement Present	9 participants n=99 Participants
Portal vein involvement Absent	15 participants n=99 Participants
Extent of cancer Unifocal	2 participants n=99 Participants
Extent of cancer Multifocal	11 participants n=99 Participants
Extent of cancer Metastatic	11 participants n=99 Participants
Prior therapy received for this cancer Transarterial chemoembolization (TACE)	4 participants receiving this prior tx n=99 Participants
Prior therapy received for this cancer Transarterial radioembolization (TARE)	2 participants receiving this prior tx n=99 Participants
Prior therapy received for this cancer Ablation	2 participants receiving this prior tx n=99 Participants
Prior therapy received for this cancer Surgery	8 participants receiving this prior tx n=99 Participants
Prior therapy received for this cancer None	12 participants receiving this prior tx n=99 Participants
Prior therapy received for this cancer Missing	1 participants receiving this prior tx n=99 Participants

PRIMARY outcome

Timeframe: 3.5 years

Outcome measures

Outcome measures
Measure	Everolimus + Pasireotide n=24 Participants 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.
Time to Progression (TTP)	3.5 months Interval 2.0 to 5.8

SECONDARY outcome

Timeframe: 3.5 years

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).

Outcome measures

Outcome measures
Measure	Everolimus + Pasireotide n=24 Participants 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.
Number of Individuals Experiencing Toxicity Dose Limiting Toxicities (DLT)	1 participants
Number of Individuals Experiencing Toxicity Any adverse event	24 participants

SECONDARY outcome

Timeframe: 3.5 years

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

Outcome measures

Outcome measures
Measure	Everolimus + Pasireotide n=24 Participants 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.
Overall Survival (OS)	6.7 months Interval 6.0 to The upper limit of the 95% Confidence Interval was calculated as infinity (and thus NA) due to few events at the time of analysis.

SECONDARY outcome

Timeframe: 3.5 years

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Everolimus + Pasireotide n=22 Participants 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.
Objective Response Rate (ORR) Radiographic response (CR or PR)	0 percentage of participants
Objective Response Rate (ORR) Stable disease	45.5 percentage of participants

Adverse Events

Everolimus + Pasireotide

Serious events: 6 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Everolimus + Pasireotide n=24 participants at risk 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.
Nervous system disorders Stroke	8.3% 2/24 • Number of events 2 • Followed for 4 weeks after treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Psychiatric disorders Confusion	4.2% 1/24 • Number of events 2 • Followed for 4 weeks after treatment
General disorders Death NOS	8.3% 2/24 • Number of events 2 • Followed for 4 weeks after treatment
Gastrointestinal disorders Diarrhea	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Nervous system disorders Dizziness	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Respiratory, thoracic and mediastinal disorders Epistaxis	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
General disorders Fatigue	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	8.3% 2/24 • Number of events 3 • Followed for 4 weeks after treatment
Hepatobiliary disorders Hepatobiliary Disorders - Other, Specify	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Metabolism and nutrition disorders Hypokalemia	8.3% 2/24 • Number of events 2 • Followed for 4 weeks after treatment
Gastrointestinal disorders Mucositis Oral	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Respiratory, thoracic and mediastinal disorders Pleural Effusion	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Gastrointestinal disorders Rectal Hemorrhage	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations Weight Loss	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment

Other adverse events

Other adverse events
Measure	Everolimus + Pasireotide n=24 participants at risk 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.
Gastrointestinal disorders Abdominal Pain	8.3% 2/24 • Number of events 3 • Followed for 4 weeks after treatment
Investigations Activated Partial Thromboplastin Time Prolonged	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations Alanine Aminotransferase Increased	41.7% 10/24 • Number of events 11 • Followed for 4 weeks after treatment
Investigations Alkaline Phosphatase Increased	41.7% 10/24 • Number of events 14 • Followed for 4 weeks after treatment
Blood and lymphatic system disorders Anemia	33.3% 8/24 • Number of events 8 • Followed for 4 weeks after treatment
Metabolism and nutrition disorders Anorexia	12.5% 3/24 • Number of events 3 • Followed for 4 weeks after treatment
Investigations Aspartate Aminotransferase Increased	54.2% 13/24 • Number of events 16 • Followed for 4 weeks after treatment
Musculoskeletal and connective tissue disorders Back Pain	8.3% 2/24 • Number of events 2 • Followed for 4 weeks after treatment
Investigations Blood Bilirubin Increased	20.8% 5/24 • Number of events 8 • Followed for 4 weeks after treatment
Cardiac disorders Chest Pain - Cardiac	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations Cholesterol High	12.5% 3/24 • Number of events 3 • Followed for 4 weeks after treatment
Psychiatric disorders Confusion	8.3% 2/24 • Number of events 2 • Followed for 4 weeks after treatment
Gastrointestinal disorders Constipation	8.3% 2/24 • Number of events 2 • Followed for 4 weeks after treatment
Respiratory, thoracic and mediastinal disorders Cough	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Gastrointestinal disorders Diarrhea	37.5% 9/24 • Number of events 10 • Followed for 4 weeks after treatment
Nervous system disorders Dysgeusia	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
General disorders Edema Limbs	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
General disorders Fatigue	29.2% 7/24 • Number of events 8 • Followed for 4 weeks after treatment
General disorders Fever	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
General disorders Flu Like Symptoms	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations Hemoglobin Increased	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Metabolism and nutrition disorders Hyperglycemia	66.7% 16/24 • Number of events 50 • Followed for 4 weeks after treatment
Vascular disorders Hypertension	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Metabolism and nutrition disorders Hypertriglyceridemia	16.7% 4/24 • Number of events 4 • Followed for 4 weeks after treatment
Metabolism and nutrition disorders Hypocalcemia	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Metabolism and nutrition disorders Hypomagnesemia	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Metabolism and nutrition disorders Hypophosphatemia	4.2% 1/24 • Number of events 2 • Followed for 4 weeks after treatment
Vascular disorders Hypotension	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Psychiatric disorders Insomnia	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Gastrointestinal disorders Lower Gastrointestinal Hemorrhage	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations Lymphocyte Count Decreased	4.2% 1/24 • Number of events 2 • Followed for 4 weeks after treatment
Gastrointestinal disorders Mucositis Oral	33.3% 8/24 • Number of events 10 • Followed for 4 weeks after treatment
Musculoskeletal and connective tissue disorders Muscle Weakness Upper Limb	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Gastrointestinal disorders Nausea	12.5% 3/24 • Number of events 5 • Followed for 4 weeks after treatment
Nervous system disorders Nervous System Disorders - Other, Specify	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations Neutrophil Count Decreased	12.5% 3/24 • Number of events 3 • Followed for 4 weeks after treatment
General disorders Pain	8.3% 2/24 • Number of events 4 • Followed for 4 weeks after treatment
Musculoskeletal and connective tissue disorders Pain In Extremity	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysesthesia Syndrome	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations Platelet Count Decreased	25.0% 6/24 • Number of events 8 • Followed for 4 weeks after treatment
Skin and subcutaneous tissue disorders Pruritus	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Skin and subcutaneous tissue disorders Rash Acneiform	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Skin and subcutaneous tissue disorders Rash Maculo-Papular	20.8% 5/24 • Number of events 6 • Followed for 4 weeks after treatment
Gastrointestinal disorders Rectal Hemorrhage	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Gastrointestinal disorders Stomach Pain	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Gastrointestinal disorders Vomiting	12.5% 3/24 • Number of events 3 • Followed for 4 weeks after treatment
Investigations Weight Loss	4.2% 1/24 • Number of events 1 • Followed for 4 weeks after treatment
Investigations White Blood Cell Decreased	8.3% 2/24 • Number of events 3 • Followed for 4 weeks after treatment

Additional Information

Dr. Hanna Sanoff

Div. of Hematology and Oncology, Univ. of North Carolina at Chapel Hill

Phone: 919-966-4431

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place