- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01488487
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
-
-
North Carolina
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Chapel Hill, North Carolina, United States, 27599
- University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
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Winston-Salem, North Carolina, United States, 27157
- Comprehensive Cancer Center of Wake Forest University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Each subject must meet all of the following inclusion criteria to participate in this study:
- 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.
- Maximum Childs-Pugh score 6 (see Appendix A) with no active encephalopathy
- Prior systemic therapy limited to sorafenib that was discontinued due to intolerance. Patients must undergo at least a 4-week washout prior to enrollment.
- Eastern Cooperative Oncology Group (ECOG) PS of 0-2
- Life expectancy of >12 weeks
- Age ≥18 years
- 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).
- Minimum of 4 weeks since any major surgery
- No active serious infection or other comorbid illness which would impair ability to participate in the trial.
- 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).
- 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.
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)
- Serum magnesium and serum potassium within institutional normal limits (patients may be on replacement)
- 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.
- 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.)
- 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:
- Patients who have received prior treatment with an mTOR inhibitor (e.g., sirolimus, temsirolimus, everolimus) or somatostatin analog (e.g. octeotride)
- 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).
- Patients with a known hypersensitivity to everolimus or other rapamycins (e.g., sirolimus, temsirolimus) or to its excipients
- Patients with a known hypersensitivity to somatostatin or to its excipients
- Concurrent or planned radiation, hormonal, chemotherapeutic, experimental, or targeted biologic therapy
- Prior treatment with any investigational drug within the preceding 4 weeks
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.
- 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
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.
- 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.
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
- Symptomatic cholelithiasis
- Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
- A known history of HIV seropositivity (HIV testing is not mandatory)
- 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.)
- 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.)
- 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
- 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
- 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.
- Inability to comply with study and/or follow-up procedures
- History of noncompliance to medical regimens
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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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.
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Everolimus 7.5 mg administered daily for 28 days per cycle until disease progression or unacceptable toxicity.
Other Names:
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Progression (TTP)
Time Frame: 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.
|
3.5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Individuals Experiencing Toxicity
Time Frame: 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).
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3.5 years
|
Overall Survival (OS)
Time Frame: 3.5 years
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Overall survival is defined as the time from study enrollment until death.
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3.5 years
|
Objective Response Rate (ORR)
Time Frame: 3.5 years
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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. |
3.5 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Hanna Sanoff, MD, University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Physiological Effects of Drugs
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Everolimus
- Somatostatin
- Pasireotide
Other Study ID Numbers
- LCCC 1032
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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