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

Sponsor
UNC Lineberger Comprehensive Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT01488487
Collaborator
Novartis Pharmaceuticals (Industry)
24
3
1
39
8
0.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
24 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Single Arm Study of Everolimus and Pasireotide (SOM230) in Patients With Advanced or Metastatic Hepatocellular Carcinoma (HCC)
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Mar 1, 2015
Actual Study Completion Date :
Mar 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: Everolimus + pasireotide

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.

Drug: Everolimus
Everolimus 7.5 mg administered daily for 28 days per cycle until disease progression or unacceptable toxicity.
Other Names:
  • Afinitor
  • RAD001
  • Drug: 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.
    Other Names:
  • SOM230
  • Pasireotide LAR
  • Pasireotide s.c.
  • Outcome Measures

    Primary Outcome Measures

    1. Time to Progression (TTP) [3.5 years]

      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.

    Secondary Outcome Measures

    1. Number of Individuals Experiencing Toxicity [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).

    2. Overall Survival (OS) [3.5 years]

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

    3. Objective Response Rate (ORR) [3.5 years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Each subject must meet all of the following inclusion criteria to participate in this study:
    1. Advanced or metastatic hepatocellular carcinoma (stage C per the BCLC criteria, see Appendix A). HCC may be diagnosed by tissue diagnosis or Alpha-fetoprotein (AFP) >400 ng/mL with compatible mass on Magnetic Resonance Imaging Scan (MRI). Cat Scan (CT) abdomen with 3-phase contrast with arterial phase enhancement is acceptable, although MRI is preferred (imaging should be done within 4 weeks of study initiation). Recurrences of previously resected HCC will not require tissue confirmation if there is clear radiographic recurrence in the judgment of the investigator. Disease must not otherwise be amenable to local therapy.

    2. Maximum Childs-Pugh score 6 (see Appendix A) with no active encephalopathy

    3. Prior systemic therapy limited to sorafenib that was discontinued due to intolerance. Patients must undergo at least a 4-week washout prior to enrollment.

    4. Eastern Cooperative Oncology Group (ECOG) PS of 0-2

    5. Life expectancy of >12 weeks

    6. Age ≥18 years

    7. Patients who have received previous local therapy, such as surgery, radiotherapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous injection, or cryoablation, will be eligible for enrollment in the study provided that there is documented progression and disease is not amenable to further local therapies. Therapy must be completed >4 weeks prior to study initiation (Day 1 of everolimus and pasireotide administration).

    8. Minimum of 4 weeks since any major surgery

    9. No active serious infection or other comorbid illness which would impair ability to participate in the trial.

    10. International Normalized Ratio (INR) ≤1.5. (Anticoagulation is allowed if target INR ≤2.0 on a stable dose of warfarin or on a stable dose of low molecular weight heparin (LMWH) for >2 weeks at time of enrollment).

    11. Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides (TGs) ≤2.5 x upper limit of normal (ULN). NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.

    12. Patients must have adequate organ function as evidenced by:

    • Absolute neutrophil count (ANC) ≥1.5 x 109/L

    • Platelet count ≥50 x 109/L

    • Hemoglobin (Hg) >9 g/dL

    • Bilirubin ≤2 x ULN

    • Aspartate transaminase (AST) or Alanine transaminase (ALT) ≤5 x ULN

    • Serum creatinine ≤1.5 x ULN OR creatinine clearance ≥50 mL/min (estimated by Cockcroft Gault or measured)

    1. Serum magnesium and serum potassium within institutional normal limits (patients may be on replacement)

    2. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test performed within 7 days prior to Day 1 of everolimus and pasireotide administration.

    3. WOCBP and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men and women should use adequate birth control for at least 8 weeks after the last administration of study drugs. (Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions and are therefore not considered effective for this study.)

    4. Signed, Institutional Review Board (IRB) approved written informed consent

    Exclusion Criteria:
    • Patients meeting any of the following exclusion criteria at baseline will be excluded from study participation:
    1. Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus) or somatostatin analog (e.g. octeotride)

    2. Chronic treatment with systemic steroids (except for intermittent topical, local injection, or eye drops) or another immunosuppressive agent. NOTE: This restriction regarding systemic steroids does not apply should patient need course of glucocorticoid for treatment of non-infectious pneumonitis during study (see Section 4.5.2).

    3. Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients

    4. Patients with a known hypersensitivity to somatostatin or to its excipients

    5. Concurrent or planned radiation, hormonal, chemotherapeutic, experimental, or targeted biologic therapy

    6. Prior treatment with any investigational drug within the preceding 4 weeks

    7. 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 (New York Heart Association [NYHA] 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 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 fasting serum glucose >1.5 x ULN or Glycated hemoglobin (HbA1c) >8.0% (Note: at the principle investigator's discretion, ineligible patients can be re-screened after adequate medical therapy has been instituted.)

    • Active (acute or chronic) or uncontrolled severe infections. NOTE: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B viral deoxyribonucleic acid (HBV DNA) and Hepatitis C viral ribonucleic acid (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. See Section 4.2 for further information.

    1. Clinically significant third space fluid accumulation (i.e., ascites requiring paracentesis despite use of diuretics) or pleural effusion that either requires thoracentesis or is associated with shortness of breath

    2. Risk factors for prolongation of Corrected QT Interval (QTc)* including:

    • QTc at screening >450 msec

    • History of syncope or family history of idiopathic sudden death

    • Sustained or clinically significant cardiac arrhythmias

    • Risk factors for Torsades de Pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade AV block

    • Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes or Parkinson's disease), human immunodeficiency virus (HIV), uncontrolled hypothyroidism, or cardiac failure

    • Concomitant medication(s) known to increase QT interval (See Appendix B)

    • University of North Carolina at Chapel Hill (UNC) uses GE electrocardiogram (ECG) carts which use the Bazett formula for QTc.

    1. Patients should not receive immunization with attenuated live vaccines within 1 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-Guérin (BCG), yellow fever, varicella, and TY21a typhoid vaccines.

    2. Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases

    3. Symptomatic cholelithiasis

    4. Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin

    5. A known history of HIV seropositivity (HIV testing is not mandatory)

    6. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection.)

    7. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except warfarin as long as the goal INR is ≤1.5). Low-molecular-weight heparin (LMWH) is permitted (see Section 3.1.10.)

    8. Unable or unwilling to discontinue use of prohibited fruit (or its juices) and/or prohibited medications listed in Appendix B for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study

    9. Male patient whose sexual partner(s) are WOCBP who are not willing to use adequate contraception during the study and for 8 weeks after the end of treatment

    10. Active alcohol intake of 80 grams or more per day. For reference, one portion of alcohol (one glass of wine, one can or bottle of beer, or one ounce of hard liquor) contains approximately 15 grams of ethanol.

    11. Inability to comply with study and/or follow-up procedures

    12. History of noncompliance to medical regimens

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Moffitt Cancer Center Tampa Florida United States 33612
    2 University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
    3 Comprehensive Cancer Center of Wake Forest University Winston-Salem North Carolina United States 27157

    Sponsors and Collaborators

    • UNC Lineberger Comprehensive Cancer Center
    • Novartis Pharmaceuticals

    Investigators

    • Principal Investigator: Hanna Sanoff, MD, University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    UNC Lineberger Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01488487
    Other Study ID Numbers:
    • LCCC 1032
    First Posted:
    Dec 8, 2011
    Last Update Posted:
    Apr 7, 2016
    Last Verified:
    Mar 1, 2016
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by UNC Lineberger Comprehensive Cancer Center
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 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.
    Arm/Group Title Everolimus + Pasireotide
    Arm/Group Description 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.
    Period Title: Overall Study
    STARTED 24
    Received Treatment 24
    COMPLETED 15
    NOT COMPLETED 9

    Baseline Characteristics

    Arm/Group Title Everolimus + Pasireotide
    Arm/Group Description 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 Participants 24
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    15
    62.5%
    >=65 years
    9
    37.5%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    59
    Sex: Female, Male (Count of Participants)
    Female
    8
    33.3%
    Male
    16
    66.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    24
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    2
    8.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    4.2%
    White
    21
    87.5%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    24
    100%
    Chronic Hepatitis C (participants) [Number]
    Present
    7
    29.2%
    Absent
    17
    70.8%
    Chronic Hepatitis B (participants) [Number]
    Present
    2
    8.3%
    Absent
    22
    91.7%
    Child-Pugh Score (Stage) (units on a scale) [Median (Full Range) ]
    Median (Full Range) [units on a scale]
    5
    Time from diagnosis to enrollment (Months) [Median (Full Range) ]
    Median (Full Range) [Months]
    4
    CLIP (Cancer of the Liver Italian Program) score (units on a scale) [Median (Full Range) ]
    Median (Full Range) [units on a scale]
    1.5
    BCLC (Barcelona Clinic Liver Cancer) Stage (participants) [Number]
    Stage B
    2
    8.3%
    Stage C
    21
    87.5%
    Missing
    1
    4.2%
    Portal vein involvement (participants) [Number]
    Present
    9
    37.5%
    Absent
    15
    62.5%
    Extent of cancer (participants) [Number]
    Unifocal
    2
    8.3%
    Multifocal
    11
    45.8%
    Metastatic
    11
    45.8%
    Prior therapy received for this cancer (participants receiving this prior tx) [Number]
    Transarterial chemoembolization (TACE)
    4
    16.7%
    Transarterial radioembolization (TARE)
    2
    8.3%
    Ablation
    2
    8.3%
    Surgery
    8
    33.3%
    None
    12
    50%
    Missing
    1
    4.2%

    Outcome Measures

    1. Primary Outcome
    Title Time to Progression (TTP)
    Description 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.
    Time Frame 3.5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Everolimus + Pasireotide
    Arm/Group Description 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.
    Measure Participants 24
    Median (95% Confidence Interval) [months]
    3.5
    2. Secondary Outcome
    Title Number of Individuals Experiencing Toxicity
    Description 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).
    Time Frame 3.5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Everolimus + Pasireotide
    Arm/Group Description 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.
    Measure Participants 24
    Dose Limiting Toxicities (DLT)
    1
    4.2%
    Any adverse event
    24
    100%
    3. Secondary Outcome
    Title Overall Survival (OS)
    Description Overall survival is defined as the time from study enrollment until death.
    Time Frame 3.5 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Everolimus + Pasireotide
    Arm/Group Description 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.
    Measure Participants 24
    Median (95% Confidence Interval) [months]
    6.7
    4. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description 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.
    Time Frame 3.5 years

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Everolimus + Pasireotide
    Arm/Group Description 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.
    Measure Participants 22
    Radiographic response (CR or PR)
    0
    0%
    Stable disease
    45.5
    189.6%

    Adverse Events

    Time Frame Followed for 4 weeks after treatment
    Adverse Event Reporting Description
    Arm/Group Title Everolimus + Pasireotide
    Arm/Group Description 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.
    All Cause Mortality
    Everolimus + Pasireotide
    Affected / at Risk (%) # Events
    Total / (NaN)
    Serious Adverse Events
    Everolimus + Pasireotide
    Affected / at Risk (%) # Events
    Total 6/24 (25%)
    Gastrointestinal disorders
    Diarrhea 1/24 (4.2%) 1
    Mucositis Oral 1/24 (4.2%) 1
    Rectal Hemorrhage 1/24 (4.2%) 1
    General disorders
    Death NOS 2/24 (8.3%) 2
    Fatigue 1/24 (4.2%) 1
    Hepatobiliary disorders
    Hepatobiliary Disorders - Other, Specify 1/24 (4.2%) 1
    Investigations
    Weight Loss 1/24 (4.2%) 1
    Metabolism and nutrition disorders
    Hypokalemia 2/24 (8.3%) 2
    Musculoskeletal and connective tissue disorders
    Generalized Muscle Weakness 2/24 (8.3%) 3
    Nervous system disorders
    Stroke 2/24 (8.3%) 2
    Dizziness 1/24 (4.2%) 1
    Psychiatric disorders
    Confusion 1/24 (4.2%) 2
    Respiratory, thoracic and mediastinal disorders
    Dyspnea 1/24 (4.2%) 1
    Epistaxis 1/24 (4.2%) 1
    Pleural Effusion 1/24 (4.2%) 1
    Other (Not Including Serious) Adverse Events
    Everolimus + Pasireotide
    Affected / at Risk (%) # Events
    Total 24/24 (100%)
    Blood and lymphatic system disorders
    Anemia 8/24 (33.3%) 8
    Cardiac disorders
    Chest Pain - Cardiac 1/24 (4.2%) 1
    Gastrointestinal disorders
    Abdominal Pain 2/24 (8.3%) 3
    Constipation 2/24 (8.3%) 2
    Diarrhea 9/24 (37.5%) 10
    Lower Gastrointestinal Hemorrhage 1/24 (4.2%) 1
    Mucositis Oral 8/24 (33.3%) 10
    Nausea 3/24 (12.5%) 5
    Rectal Hemorrhage 1/24 (4.2%) 1
    Stomach Pain 1/24 (4.2%) 1
    Vomiting 3/24 (12.5%) 3
    General disorders
    Edema Limbs 1/24 (4.2%) 1
    Fatigue 7/24 (29.2%) 8
    Fever 1/24 (4.2%) 1
    Flu Like Symptoms 1/24 (4.2%) 1
    Pain 2/24 (8.3%) 4
    Investigations
    Activated Partial Thromboplastin Time Prolonged 1/24 (4.2%) 1
    Alanine Aminotransferase Increased 10/24 (41.7%) 11
    Alkaline Phosphatase Increased 10/24 (41.7%) 14
    Aspartate Aminotransferase Increased 13/24 (54.2%) 16
    Blood Bilirubin Increased 5/24 (20.8%) 8
    Cholesterol High 3/24 (12.5%) 3
    Hemoglobin Increased 1/24 (4.2%) 1
    Lymphocyte Count Decreased 1/24 (4.2%) 2
    Neutrophil Count Decreased 3/24 (12.5%) 3
    Platelet Count Decreased 6/24 (25%) 8
    Weight Loss 1/24 (4.2%) 1
    White Blood Cell Decreased 2/24 (8.3%) 3
    Metabolism and nutrition disorders
    Anorexia 3/24 (12.5%) 3
    Hyperglycemia 16/24 (66.7%) 50
    Hypertriglyceridemia 4/24 (16.7%) 4
    Hypocalcemia 1/24 (4.2%) 1
    Hypomagnesemia 1/24 (4.2%) 1
    Hypophosphatemia 1/24 (4.2%) 2
    Musculoskeletal and connective tissue disorders
    Back Pain 2/24 (8.3%) 2
    Muscle Weakness Upper Limb 1/24 (4.2%) 1
    Pain In Extremity 1/24 (4.2%) 1
    Nervous system disorders
    Dysgeusia 1/24 (4.2%) 1
    Nervous System Disorders - Other, Specify 1/24 (4.2%) 1
    Psychiatric disorders
    Confusion 2/24 (8.3%) 2
    Insomnia 1/24 (4.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough 1/24 (4.2%) 1
    Dyspnea 1/24 (4.2%) 1
    Skin and subcutaneous tissue disorders
    Palmar-Plantar Erythrodysesthesia Syndrome 1/24 (4.2%) 1
    Pruritus 1/24 (4.2%) 1
    Rash Acneiform 1/24 (4.2%) 1
    Rash Maculo-Papular 5/24 (20.8%) 6
    Vascular disorders
    Hypertension 1/24 (4.2%) 1
    Hypotension 1/24 (4.2%) 1

    Limitations/Caveats

    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.

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Hanna Sanoff
    Organization Div. of Hematology and Oncology, Univ. of North Carolina at Chapel Hill
    Phone 919-966-4431
    Email hanna_sanoff@med.unc.edu
    Responsible Party:
    UNC Lineberger Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT01488487
    Other Study ID Numbers:
    • LCCC 1032
    First Posted:
    Dec 8, 2011
    Last Update Posted:
    Apr 7, 2016
    Last Verified:
    Mar 1, 2016