Dose-defining Study of Tirapazamine Combined With Embolization in Liver Cancer

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase 1 study is to determine the optimal dose and tolerability of a hypoxia-activating agent, tirapazamine, when it is combined with embolization in liver cancer. Liver cancer patients who are Child-Pugh score A, suitable for embolization with tumor no more than 4 nodules are eligible. Tirapazamine will be given by intra-arterial injection before embolization. Treatment effect is evaluated by MRI based on mRECIST criteria. Repeat treatment is necessary only if disease progression. Expansion cohorts are open for metastatic gastrointestinal cancer and neuroendocrine tumor.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Teclison Ltd.
• Treatments: Tirapazamine

Criteria

• Confirmed diagnosis of HCC > 10 mm with a characteristic 4-phase CT or dynamic contrast enhanced MRI finding showing intense arterial uptake followed by "washout" of contrast in the venous-delayed phases per American Association for the Study of Liver Disease (AASLD) criteria.

• Patients between ages 20 and 80

• Patients with single or multiple (2-4 nodules) HCC who are unsuitable or unwilling for surgical resection or RFA. The largest tumor nodule should be less than 10 cm in the largest diameter. The total volume of tumor cannot exceed 50% of liver; or patients with liver metastatic gastrointestinal cancer, including neuroendocrine tumor

• Patients are candidates for TAE or Transarterial ChemoEmbolization (TACE). No tumor invasion to portal vein or thrombosis in portal vein.

• ECOG score 0-1 with no known cardiac, pulmonary or renal dysfunction

• Child-Pugh score group A or B7 liver functional score

• Prior local therapies such as surgical resection, radiofrequency ablation, or alcohol injection are allowed as long as tumor progresses from the prior treatment and the patients are still candidates for TAE. All prior therapy must be at least 4 weeks prior to enrollment and free from treatment-related toxicity.

• No TAE/TACE in the past

• Patients have normal organ function: ANC ≥ 1000 /µL, Hemoglobin ≥ 9 gm/dL, Platelets ≥ 50,000 /µL, Creatinine ≤ 2 mg/dL, AST and ALT < 5 X upper normal limit of the current institution; bilirubin ≤ 3.0 mg/dL, PT prolongation no more than 4 sec above upper limit of normal.

For the expansion cohort of neuroendocrine tumor or metastatic solid tumor with liver involvement

• Unresectable, locally advanced or metastatic, well differentiated (low or intermediate grade), neuroendocrine tumors (NET).

• Metastatic solid tumor with liver involvement.