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

Study Purpose

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. Dose escalation cohort has been completed. Expansion cohort is open for metastatic liver dominant neuroendocrine tumor.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	20 Years - 99 Years
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Patients with well-differentiated NET and liver-dominant metastatic disease with intrahepatic disease progression, regardless of primary tumor origin or tumor functional status. Patients may have extrahepatic lesions as long as the majority of the disease burden is intrahepatic. 2. No limitation in hepatic lesion tumor size or number but the total volume of liver tumors cannot exceed 50% of the liver volume. 3. Patients are allowed to have prior US Food and Drug Administration (FDA)-approved treatments, including systemic therapies, surgery, ablation, or transarterial therapies for the metastatic NET. 4. Age 20 or higher, ECOG functional status 0-1, and with no known major cardiac, pulmonary, or renal dysfunction. 5. Are candidates for TAE or TACE and without portal vein occlusion per treating interventional radiologists. 6. ANC no less than 1000 /μL. Hemoglobin ≥ 9 gm/dL. Platelets no less than 50,000 /μL. Creatinine no more than 2.0 mg/dL. AST, ALT no more than 5X upper limit of normal. Bilirubin no more than 2.5 mg/dl. PT prolongation ≤ 4 sec above upper limit of normal. 7. Woman of child-bearing potential (WOCBP) should use highly effective contraception during trial participation and for 6 months after the last dose of tirapazamine and men who are partners with WOCBP should use highly effective contraception, including barrier contraception, during trial participation and for 3 months after the last dose of tirapazamine.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02174549
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Teclison Ltd.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Michael Soulen, MD
Principal Investigator Affiliation	Univ. of Pennsylvania
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Hepatocellular Carcinoma, Gastrointestinal Cancer Metastatic, Neuroendocrine Tumors
Study Website:	View Trial Website

Additional Details

The study is a 3+3 design for dose escalation. Each cohort will have 3-6 patients based on tolerability. Patients will receive escalated doses of tirapazamine until maximally tolerated dose. Embolization is performed per standard practice using Lipiodol and Gelfoam under X-ray guidance. Once a suitable dose is determined, an expansion cohort of 15 patients will be treated with the recommended phase 2 dose to determine preliminary efficacy. Expansion cohorts include

(1) hepatocellular carcinoma, (2) metastatic solid tumors with liver metastasis, and (3) neuroendocrine tumor.

Adverse events are evaluated by CTCAE vs.#46; 5.0 and efficacy is evaluated by MRI using modified RECIST criteria and RECIST criteria. The dose escalation part has been completed. Only the third cohort or neuroendocrine tumor remains active for future patient enrollment.

Arms & Interventions

Arms

Experimental: Tirapazamine

Intra-arterial administration with tirapazamine before embolization to evaluate the response in metastatic liver lesions of NET

Interventions

Drug: - Tirapazamine

Intra-arterial injection into the tumor feeding artery

Procedure: - Conventional Transarterial Embolization (TAE)

Lipiodol and Gelfoam used to embolize tumor vessels and induce tumor hypoxia

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Stanford University, Palo Alto, California

Status

Recruiting

Address

Stanford University

Palo Alto, California, 94305

Site Contact

Mikayla Easterling

[email protected]

650-724-3698

University of Pennsylvania, Philadelphia, Pennsylvania

Status

Recruiting

Address

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Site Contact

Veronica Faris

[email protected]

215-573-9765

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