Neoplasms

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Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

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Hematinics

Doxorubicin

Liposomal doxorubicin

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The dose of TH-302 will be mixed with doxorubicin 50mg to use as the chemoembolization mixture for transarterial chemoembolization (TACE).

Phase I Dose level -1

Phase I dose level 1

Phase I Dose level 2

Phase I Dose level 3

Alain Perez

Darren S Sigal, M.D.

Darren S Sigal, MD

The primary objective of this phase I dose escalation study is to determine the maximum tolerated dose of TH-302 when administered with doxorubicin via trans-arterial chemo-embolization (TACE) in patients with hepatocellular carcinoma (HCC) who are not transplant candidates and have unresectable disease. HCC is the second leading cause of worldwide cancer death and is generally incurable without liver transplant. TACE can convert about 40% of these patients to transplant candidates. Additionally, in non-transplant HCC patients, TACE confers statistical improvements in overall survival. Selective HCC arterial catheterization during TACE allows for the delivery of concentrated drugs to the liver tumor but the optimal TACE chemotherapy regimen has not yet been determined. TH-302 is a hypoxia inducible agent that can be activated in the hypoxic environment induced by TACE.

Transarterial chemoembolization (TACE) is the major modality utilized for tumor downstaging for transplant and for local therapy in non-transplant patients. This procedure allows delivery of concentrated drugs to the tumor, followed by embolization that eliminates its blood supply creating an environment of hypoxia. The process induces tumor ischemia, while achieving a drug concentration in the tumor 10 to 25 times greater than can be achieved by infusion.

A hypoxic microenvironment is a characteristic of many solid tumors including hepatocellular cancer, further induced by TACE. The hypoxia-activated prodrug, TH-302, is designed to selectively physiologically target the hypoxic microenvironment. While doxorubicin and cisplatin have been used as the drugs in TACE among other agents, none have stood out as the optimal agent in targeting HCC. Because of the action of TH-302 in hypoxia, this agent has a mechanistic advantage as a agent in TACE.

The current study is designed to assess the potential therapeutic benefit of adding TH-302 to the standard doxorubicin based TACE regimen in patients with advanced hepatocellular carcinomas.

TH-302 Plus Doxorubicin Delivered by Trans-Arterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma

A Phase I Dose Escalation Study of TH-302 Plus Doxorubicin Delivered by Trans-Arterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma

Maximum tolerated dose (MTD) of TH-302 when co-administered with doxorubicin via TACE in patients with advanced hepatocellular cancer will be assessed with a Fibonacci (3+3) dose escalation design.

Assess overall response rate using standard RECIST criteria measured by triple phase CT or MRI at least 6 weeks post TACE administration

Threshold Pharmaceuticals

Scripps Clinic Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
TH-302 Plus Doxorubicin Delivered by Trans-Arterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma	NCT01721941	Hepatocellular ...	Phase I Dose le... Phase I dose le... Phase I Dose le... Phase I Dose le...	18 Years -	Scripps Clinic Cancer Center
TH-302 Plus Doxorubicin Delivered by Trans-Arterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma	NCT01721941	Hepatocellular ...	Phase I Dose le... Phase I dose le... Phase I Dose le... Phase I Dose le...	18 Years -	Scripps Clinic Cancer Center

Spots Global Cancer Trial Database for phase i dose level 2