Clinical trial NCT03008512: A Phase II Study of Weekly Genexol-PM in Patients With Hepatocelluar Carcinoma After Failure of Sorafenib
Official title: A Phase II Study of Weekly Genexol-PM in Patients With Advanced Hepatocelluar Carcinoma After Failure of Sorafenib
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: Liver Neoplasms
Antineoplastic Agents
Carcinoma, Hepatocellular
Genexol-PM
Neoplasms by Site
Sorafenib
Liver Diseases
Digestive System Neoplasms
Lead sponsor: Gachon University Gil Medical Center
Sponsor class: OTHER
First posted: 2017-01-02
Enrollment: 5
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study evaluate activity and safety profile of weekly Genexol-PM in patients with advanced hepatocellular carcinoma for whom sorafenib treatment failed. Patients will receive Genexol-PM on days 1, 8, and 15 every 4 weeks.

Detailed description: Hepatocelluar carcinoma (HCC) is a highly vascular neoplasm characterized by arterial enhancement on CT or MRI. Angiogenesis provides a target for novel prognostic and therapeutic approaches to HCC. Sorafenib is the standard 1st-line therapy shown to significantly improve overall survival in advanced HCC. However, sorafenib benefits are mostly transient and modest. In addition, sorafenib is associated with major toxicities, and about 30% of patients stop it because of intolerance. Effective therapies are needed for patients who experience progression during or after receiving sorafenib or who have sorafenib intolerance. Paclitaxel has an antiagiogenic activity and weekly administration of paclitaxel is considered to have enhanced efficacy over 3-weekly administration due to greater drug exposure or a direct antiangiogenic effect. A previous phase I study showed that weekly paclitaxel has activity in hepatocellular carcinoma and further investigation in phase II trials is warranted. Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, is believed to be superior to conventional paclitaxel in terms of the obviation of premedication and the delivery of higher paclitaxel doses without additional toxicity.

Eligibility criteria: Inclusion Criteria:

1. A diagnosis of hepatocellular carcinoma (HCC) based on either

   1. histopathologic or cytologic findings
   2. a diagnosis of cirrhosis and HCC with classical imaging characteristics (at least a 3-phase liver protocol CT or MRI and a lesion that demonstrates arterial enhancement and washes out in the venous phase)
2. Previous sorafenib treatment for at least 14 days and discontinuation of sorafenib treatment prior to inclusion
3. Radiologic confirmation of disease progression during or after discontinuation of sorafenib treatment or discontinuation of sorafenib due to intolerance despite appropriate supportive care
4. Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B disease not amenable to locoregional therapy or refractory to locoregional therapy
5. ≥ 1 measurable lesion according to RECIST Version 1.1
6. ≥ 20 year of age
7. ECOG performance status ≤ 2
8. Child-Pugh score ≤ 7
9. Informed consent prior to study
10. Adequate organ function

    1. Hepatic: bilirubin ≤ 1.5 times upper limit of institutional normal value (ULN), AST or ALT ≤ 5 x ULN
    2. Renal: estimated creatinine clearance ≥ 60 mL/min
    3. Hematologic: hemoglobin ≥ 9 g/dL, absolute neutrophil count (ANC) ≥ 1,500/μL, platelets ≥ 75,000/μL (In case of thrombocytopenia associated with hypersplenism in chronic liver disease, platelets ≥ 50,000/μL is allowed for participation at the physician's discretion.)
    4. Coagulation: prothrombin time (INR) ≤ 1.5, partial thrombin time (PTT) ≤ 5 seconds above the ULN

Exclusion Criteria:

1. Previous systemic chemotherapy for advanced disease (except previous biologic agents including VEGF inhibitors, TGF-beta inhibitors, or PD-1/PD-L1 blockers)
2. A history o f or current hepatic encephalopathy or clinically meaningful ascites
3. Grade 2 or more peripheral neuropathy
4. Prior liver transplant
5. History of any other cancer within 2 years (Patients with carcinoma in situ of any origin and patients with prior malignancy who are in remission and whose likelihood of recurrence is very low, may be eligible.)
6. A history of treatment with taxanes (paclitaxel or docetaxel)
7. Females who are pregnant or lactating
8. A know allergy or hypersensitivity reaction to any of the treatment components
9. Serious preexisting medical conditions that cannot adequately controlled with appropriate therapy

Primary outcomes:
measure: Progression-free survival rate at 6 months
timeFrame: Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)
Secondary outcomes:
measure: Progression-free survival
timeFrame: Baseline to Objective Progression or Death from Any Cause (Approximately 12 Months)
measure: Overall survival
timeFrame: Baseline to Death from Any Cause (Approximately 12 Months)
measure: Objective response rate
timeFrame: Baseline to Objective Progression (Approximately 12 Months)
measure: Adverse events
timeFrame: Cycle 1 through Follow Up (Approximately 12 Months)
Other outcomes:
Locations:
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Gachon University Gil Medical Center
name: Dong Bok Shin, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, Kim NK, Bang YJ. Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 2004 Jun 1;10(11):3708-16. doi: 10.1158/1078-0432.CCR-03-0655.
citation: Strumberg D, Erhard J, Harstrick A, Klaassen U, Muller C, Eberhardt W, Wilke H, Seeber S. Phase I study of a weekly 1 h infusion of paclitaxel in patients with unresectable hepatocellular carcinoma. Eur J Cancer. 1998 Jul;34(8):1290-2. doi: 10.1016/s0959-8049(98)00054-9.
citation: Bocci G, Di Paolo A, Danesi R. The pharmacological bases of the antiangiogenic activity of paclitaxel. Angiogenesis. 2013 Jul;16(3):481-92. doi: 10.1007/s10456-013-9334-0. Epub 2013 Feb 7.
citation: Baird RD, Tan DS, Kaye SB. Weekly paclitaxel in the treatment of recurrent ovarian cancer. Nat Rev Clin Oncol. 2010 Oct;7(10):575-82. doi: 10.1038/nrclinonc.2010.120. Epub 2010 Aug 3.