Back to resultsThe Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for HCC
Primary Purpose
Advanced Hepatocellular Carcinoma (HCC)
Status
Completed
Phase
Phase 1
Locations
Taiwan
Study Type
Interventional
Intervention
Axitinib
Radiation
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Hepatocellular Carcinoma (HCC)
Eligibility Criteria
Inclusion Criteria:
- Age of 20-85 years, with ECOG performance 0-2.
- Advanced hepatocellular carcinoma (HCC), histologically or clinically diagnosed. (Multiple tumors, portal vein thrombosis, nodal metastasis or distant metastasis is allowed.)
- Unsuitable for resection, liver transplantation, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE), or recurrent / refractory after prior local-regional treatment.
- ≥ One measurable tumor.
- Child-Pugh score A or B.
Patients who fulfill all of the following criteria:
- Serum total bilirubin ≤ 3 mg/dL
- Serum alanine transaminase (ALT) ≤ 5 times ULN
- INR ≤ 2.20
- Platelet count ≥ 50,000 /mm3
- WBC count ≥ 3,000 /mm3 or ANC ≥ 1,500 /mm3
- Serum creatinine ≤ 2.0 mg/dL
- Normal thyroid function confirmed.
- Absence of grant for sorafenib.
- Sorafenib failure or intolerability (if ever used).
Exclusion Criteria:
- Considered to have high risk of bleeding (e.g. active peptic ulcer, unstable esophageal/gastric varices, history of aneurysm, and requirement of anticoagulant therapy).
- Pre-existing uncontrolled hypertension (systolic >140 mmHg, diastolic >90 mmHg) or proteinuria ≧500 mg/24 hours.
- Prior history of coronary artery disease.
- The patient is participating in other clinical trials.
- Pregnant women.
- Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
- Patients with non-healing wound.
- Requiring the use of potent CYP3A4/5 inhibitors or inducers (see Appendix).
- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Sites / Locations
- Shin Kong Wu Ho-Su Memorial Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Axitinib
Arm Description
Combined axitinib and radiotherapy (fixed strength)
Outcomes
Primary Outcome Measures
The maximal tolerated dose (MTD)
To determine the maximal tolerated dose (MTD) of axitinib in combination with RT for advanced HCC.
Secondary Outcome Measures
Full Information
NCT ID
NCT02814461
First Posted
June 23, 2016
Last Updated
September 19, 2019
Sponsor
Shin Kong Wu Ho-Su Memorial Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02814461
Brief Title
The Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for HCC
Official Title
A Phase I Clinical Trial Evaluating the Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for Advanced Hepatocellular Carcinoma (HCC)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
November 2015 (Actual)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
November 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shin Kong Wu Ho-Su Memorial Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To determine the maximal tolerated dose (MTD) of axitinib in combination with RT for advanced HCC.
Detailed Description
The goal of this study is to conduct a phase I clinical trial evaluating the safety and MTD of axitinib in combination with RT for advanced HCC. There are some rationales of conducting this clinical trial. Firstly, there is evidence of benefit from the combination of a variety of anti-angiogenic agents with RT at the pre-clinical level. Numerous pre-clinical models have documented improved outcome with the combination of RT (e.g. bevacizumab ... etc). Potential increasing the oxygenation of tumors with anti-angiogenesis is also expected to improve the therapeutic ratio of radiation therapy to hypervascular caner like HCC. Secondly, spatial cooperation may exist between local treatment (e.g. RT) and systemic therapy (e.g. axitinib). From the experience of sorafenib, the majority of patients eventually progress within the liver and die of liver failure, providing rationale to use local therapies like RT. On the other hand, from the experience of RT, the most common site of first recurrence was in the liver outside the irradiated volume, providing rationale for studies combining regional or systemic therapies with RT. Thirdly, clinical experiences with RT and anti-angiogenic agent are few but still exist with encouraging results. For example, one retrospective review from Taiwan with advanced HCC treated with RT and sunitinib (a TKI with similar mechanisms as sorafenib) reported objective response rate of 74% and a median survival of 16 months, and concluded hypofractionated RT and sunitinib can be delivered safely in HCC patients, which was compatible with the result of several phase I or II studies using sorafenib plus. Fourthly, the safety and MTD of axitinib combined with RT is needed to be established before launch of a phase II study
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Hepatocellular Carcinoma (HCC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Axitinib
Arm Type
Experimental
Arm Description
Combined axitinib and radiotherapy (fixed strength)
Intervention Type
Drug
Intervention Name(s)
Axitinib
Other Intervention Name(s)
Inlyta
Intervention Description
Axitinib (dose escalation): for total 8 weeks during and after RT, with starting dose of 1mg BID. According to the rule of traditional 3 + 3 design, 3-level axitinib dose escalation will be conducted: 1mg BID (level - I), 2mg BID (level - II) and 3mg BID (level - III).
Intervention Type
Radiation
Intervention Name(s)
Radiation
Intervention Description
Radiotherapy (RT) dose (fixed strength for normal liver): 37.5 to 67.5 Gy in 15 fractions (2.5 to 4.5 Gy per fraction) to liver tumor(s) (e.g. portal vein thrombosis, tumors with size ≥3 cm, or recurrent/refractory tumors). The final prescribed dose is based on an upper limit of mean liver dose of 18 Gy for all plans. (Daily Entecavir 0.5-1mg or Telbivudine 600mg is recommended for patients with positive hepatitis B during and 3 months after RT.)
Primary Outcome Measure Information:
Title
The maximal tolerated dose (MTD)
Description
To determine the maximal tolerated dose (MTD) of axitinib in combination with RT for advanced HCC.
Time Frame
Within 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age of 20-85 years, with ECOG performance 0-2.
Advanced hepatocellular carcinoma (HCC), histologically or clinically diagnosed. (Multiple tumors, portal vein thrombosis, nodal metastasis or distant metastasis is allowed.)
Unsuitable for resection, liver transplantation, radiofrequency ablation (RFA) or transarterial chemoembolization (TACE), or recurrent / refractory after prior local-regional treatment.
≥ One measurable tumor.
Child-Pugh score A or B.
Patients who fulfill all of the following criteria:
Serum total bilirubin ≤ 3 mg/dL
Serum alanine transaminase (ALT) ≤ 5 times ULN
INR ≤ 2.20
Platelet count ≥ 50,000 /mm3
WBC count ≥ 3,000 /mm3 or ANC ≥ 1,500 /mm3
Serum creatinine ≤ 2.0 mg/dL
Normal thyroid function confirmed.
Absence of grant for sorafenib.
Sorafenib failure or intolerability (if ever used).
Exclusion Criteria:
Considered to have high risk of bleeding (e.g. active peptic ulcer, unstable esophageal/gastric varices, history of aneurysm, and requirement of anticoagulant therapy).
Pre-existing uncontrolled hypertension (systolic >140 mmHg, diastolic >90 mmHg) or proteinuria ≧500 mg/24 hours.
Prior history of coronary artery disease.
The patient is participating in other clinical trials.
Pregnant women.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Patients with non-healing wound.
Requiring the use of potent CYP3A4/5 inhibitors or inducers (see Appendix).
Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Facility Information:
Facility Name
Shin Kong Wu Ho-Su Memorial Hospital
City
Taipei
ZIP/Postal Code
11101
Country
Taiwan
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
33472666
Citation
Yang KL, Chi MS, Ko HL, Huang YY, Huang SC, Lin YM, Chi KH. Axitinib in combination with radiotherapy for advanced hepatocellular carcinoma: a phase I clinical trial. Radiat Oncol. 2021 Jan 20;16(1):18. doi: 10.1186/s13014-020-01742-w.
Results Reference
derived
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The Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for HCC
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