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

NCT01488487 | Completed Phase 2 Results DMC

• 1 other identifier: LCCC 1032
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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.

Conditions

Advanced Adult Hepatocellular Carcinoma

Keywords

HCC; Advanced Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Time to Progression (TTP)

  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 Outcomes (3)

• Number of Individuals Experiencing Toxicity

  3.5 years

• Overall Survival (OS)

  3.5 years

• Objective Response Rate (ORR)

  3.5 years

Study Arms (1)

Everolimus + pasireotide

EXPERIMENTAL

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; Drug: Pasireotide

Interventions

Everolimus DRUG

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

Also known as: Afinitor, RAD001

Everolimus + pasireotide

Pasireotide DRUG

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.

Also known as: SOM230, Pasireotide LAR, Pasireotide s.c.

Everolimus + pasireotide

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (3)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Related Links

• UNC Lineberger Website

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Everolimus; pasireotide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and 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.

Results Point of Contact

• Title: Dr. Hanna Sanoff
• Organization: Div. of Hematology and Oncology, Univ. of North Carolina at Chapel Hill

hanna_sanoff@med.unc.edu

919-966-4431

Study Officials

• Hanna Sanoff, MD

  University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2011
• First Posted: December 8, 2011
• Study Start: December 1, 2011
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: April 7, 2016
• Results First Posted: April 7, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)