Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis

A Phase I/II, Dose-escalation Study of Lipotecan Based Concurrent Chemoradiotherapy in Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis

This is a phase I/II dose-escalation study of lipotecan based concurrent chemoradiotherapy in hepatocellular carcinoma with portal vein tumor thrombosis.

Study Overview

• Status: Terminated
• Conditions: HepatoCellular Carcinoma; Portal Vein Tumor Thrombosis
• Intervention / Treatment: Drug: Lipotecan

Detailed Description

Protocol number: TLCTLC388A1008

Primary objective:

To evaluate the safety and tolerability, including maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), of Lipotecan based concurrent chemoradiotherapy (CCRT) in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) unsuitable for local treatment.

Secondary Objective:

The secondary objective is to explore the efficacy of Lipotecan based CCRT in patients with HCC and PVTT and the effect on quality of life.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Taipei Veteran General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hosipital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients will be males or females

   • ≥20 years of age in Taiwan
   • ≥18 years old in China
2. Patients with histologically confirmed HCC or patients who do not have histological diagnosis, but the lesion is larger than 1 cm in a cirrhotic liver with typical HCC image of contrast enhanced CT scan or MRI. If the image characteristic is not typical of HCC, another contrast enhanced image modality should be confirmed for diagnosis.
3. Patients with PVTT (BCLC stage C) who are not suitable for local therapies
4. Patients with a measureable targeting lesion
5. Patients with an anticipated residual life expectancy ≥3 months
6. Patients who have adequate organ function
7. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2
8. Patients who are willing to follow birth control requirements during the study treatment and continue until 2 months after the completion of study treatment
9. Patients willing and able to comply with the study procedures and to sign a written ICF

Exclusion Criteria:

1. Patients with infiltrative type HCC
2. Patients with evidence of any extrahepatic metastasis, including but not limited to inferior vena cava thrombosis, bone metastasis, brain metastasis, or regional lymph node metastasis
3. Patients with a history of West Haven criteria grade III-IV hepatic encephalopathy or ascites
4. Patients with a history of other malignancy except primary HCC within 3 years prior to the screening visit, excluding skin squamous cell carcinoma or basal cell carcinoma
5. Patients who fail to follow the radiation dose constraint in any critical organ in the radiotherapy planning
6. Patients with an inadequately defined hepatic tumor margin for RT planning on MRI or CT that may impact treatment or safety based on investigator's judgment
7. Patients who have experienced significant allergy or hypersensitivity to the contrast medium for CT or MRI that makes it unsafe to perform the delineation for RT planning
8. Patients with a history of liver transplantation
9. Patients with a significant concurrent disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lipotecan based chemoradiotherapy; Patients will receive Lipotecan based CCRT. Lipotecan will be given as a 30-minute (±3 minutes) iv infusion qw for 6 weeks at the predefined dose level for each cohort. A total of 6 doses of Lipotecan will be administered to each patient in conjunction with RT at 3.5 Gy per fraction for 16 fractions. During CCRT period, Lipotecan should be given within 2 hours prior to the start of RT, and the Lipotecan and RT should be delivered on the same day, unless any conditions fulfils with the dose interruption standards. Radiotherapy treatment, at the allocated dose level, is only permitted if the normal tissue dose constrain criteria are maintained

Drug: Lipotecan; Lipotecan based concurrent chemoradiotherapy; Other Names: TLC388

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose determination for Lipotecan based CCRT	To determine maximum tolerated dose for Lipotecan based CCRT in HCC patients with portal vein tumor thrombosis	3 months
Best objective response evaluation of portal vein tumor thrombosis	To evaluate the best objective response rate of portal vein tumor thrombosis	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion rate (CR) of portal vein tumor thrombosis	To evaluate the conversion rate (CR rate) of PVTT	1 year
Best overall response of overall disease	To evaluate the best overall response rate of overall disease	1 year
Disease control rate of portal vein tumor thrombosis, liver tumors and overall disease	To evaluate DCR of PVTT, liver tumors (target lesions), and overall disease	1 year
Time to progression of overall disease	To evaluate the TTP of overall disease after the start of concomitant Lipotecan based CCRT	1 year
Progression free survival of overall disease	To evaluate the PFS of overall disease after the start of concomitant Lipotecan based CCRT	1 year
Overall survival of overall disease	To evaluate the OS after the start of concomitant Lipotecan based CCRT	1 year

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2017
• Primary Completion (Actual): October 31, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (Estimate): January 27, 2017

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 4, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma; Chemoradiotherapy; Portal vein tumor thrombosis; TLC388; Lipotecan
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Embolism and Thrombosis; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Thrombosis
• Other Study ID Numbers: TLC388A1008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No