Phase II Trial of SOM230 (Pasireotide LAR) in Patients With Unresectable Hepatocellular Carcinoma (HCC)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Lynn Feun
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Disease Control Rate (DCR)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The hypothesis of this clinical trial is that hepatocellular carcinomas contain somatostatin receptors which make them sensitive to the inhibitory effects of a new somatostatin analog, SOM230. This analog has greater and broader binding affinity to somatostatin receptors compared to the current drug in use, sandostatin LAR. Thus, SOM230 has the potential to be more effective in the treatment of patients with hepatocellular carcinoma.
Detailed Description
For all patients, SOM230 will be given at a starting dose of 60 mg intramuscularly (IM) every 28 days. Dose reduction will be allowed for toxicities which are deemed to be therapy-related. Patients will receive SOM230C (IM) as an outpatient and will be observed for at least 30 minutes for any immediate adverse reactions. Toxicity checks will be done every 2 weeks and laboratory tests every 4 weeks during study therapy). Safety and efficacy will be assessed throughout the treatment period. Toxicities will be graded using the Common Terminology Criteria for Adverse Events, version 4.02. Therapy will continue for maximum of two years if the patient shows no evidence of disease progression or intolerable toxicity. After completion of all study related therapy patients will complete a 30 day safety follow up visit. Patients who are still benefiting from therapy after two years may continue longer only after discussion between the Principal Investigator (PI) and the drug sponsor.
Investigators
Lynn Feun
Professor
University of Miami
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of unresectable HCC by either:
- •Histopathology or
- •Elevated serum Alpha-fetoprotein (AFP) \>400 ng/ml and findings on magnetic resonance imaging (MRI) or CT scans characteristic of a primary liver tumor.
- •Findings on MRI or CT scans characteristic of a primary liver tumor in patients with cirrhosis
- •Tumors at least 1 cm or greater
- •Age ≥ 18 years.
- •Minimum of four weeks since any major surgery, completion of radiation,or completion of all prior systemic anticancer therapy (adequately recovered from the acute toxicities of any prior therapy).
- •Patients may have progressed on sorafenib or refused or were intolerant of sorafenib. A maximum of 2 prior lines of systemic therapy (including chemotherapy or targeted therapy) will be allowed. Prior locoregional therapy such as surgery, radiofrequency ablation or transarterial chemoembolization are also allowed (these will not be counted as systemic therapy), provided that progression has been documented after these therapies, and at least 4 weeks have elapsed since the last therapy.
- •Karnofsky performance status (KPS) of 80 or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy 12 weeks or more.
Exclusion Criteria
- •Prior octreotide therapy or any somatostatin analog.
- •Chronic treatment with systemic steroids or another immunosuppressive agent.
- •Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry (ie. within 1 week of signing the informed consent).
- •Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
- •Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.
- •Patients with uncontrolled diabetes mellitus (defined as HgA1c \> 7% or =8% despite therapy) or a fasting plasma glucose \> 1.5 ULN. Note: At the principle investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted.
- •Patients with symptomatic cholelithiasis
- •Patients who have congestive heart failure (NYHA Class III or IV), unstable angina,sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block or a history of acute myocardial infarction within the six months preceding enrollment.
- •Patients who are at high risk for cardiac arrhythmias as defined by any of the following:
- •Baseline QTcF \> 470 msec
Outcomes
Primary Outcomes
Disease Control Rate (DCR)
Time Frame: At least 2 cycles, about 8 weeks
The disease-control rate (DCR) is defined as the proportion of participants achieving a best overall response of complete response (CR), partial response or stable disease (SD) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by MRI or CT Scan, and that is maintained for at least 8 weeks. CR is defined as disappearance of all target lesions; PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; and SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Secondary Outcomes
- Rate of Progression-Free Survival (PFS):(From Enrollment Until Study Completion, Approximately 3 Years)
- Rate of Overall Survival (OS)(From Enrollment Until Study Completion, Approximately 3 Years)
- Overall Response Rate (ORR)(Up to 2 Years)
- Duration of Overall Response(Up to 2 Years)
- Toxicity Profile of Protocol Therapy(Up to 2 Years)