The Safety and Maximum Tolerated Dose of Axitinib in Combination With Radiotherapy for HCC

NCT02814461 | Completed Phase 1

• 1 other identifier: 20150704M
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the maximal tolerated dose (MTD) of axitinib in combination with RT for advanced HCC.

Conditions

Advanced Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (1)

• The maximal tolerated dose (MTD)

  To determine the maximal tolerated dose (MTD) of axitinib in combination with RT for advanced HCC.

  Within 12 weeks

Study Arms (1)

Axitinib

EXPERIMENTAL

Combined axitinib and radiotherapy (fixed strength)

Drug: Axitinib; Radiation: Radiation

Interventions

Axitinib DRUG

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).

Also known as: Inlyta

Axitinib

Radiation RADIATION

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.)

Axitinib

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shin Kong Wu Ho-Su Memorial Hospital: lead

Study Sites (1)

Shin Kong Wu Ho-Su Memorial Hospital

Taipei, 11101, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 33472666 DERIVED

MeSH Terms

Interventions

Axitinib; Radiation

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Physical Phenomena

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2016
• First Posted: June 27, 2016
• Study Start: November 1, 2015
• Primary Completion: November 1, 2018
• Study Completion: November 1, 2018
• Last Updated: September 23, 2019

Record last verified: 2019-09

Locations

TW (1)