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

NCT01721941 | Unknown Phase 1 DMC

• 1 other identifier: TH302 TACE
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; HCC; liver cancer; hepatoma; TACE; transarterial chemoembolization; TH302

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of TH-302 use in TACE

  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.

  33 weeks

Secondary Outcomes (1)

• Objective response rate

  12 months

Study Arms (4)

Phase I dose level -1

EXPERIMENTAL

TH-302 25mg; Doxorubicin 50mg

Drug: Phase I Dose level -1

Phase I Dose level 1

EXPERIMENTAL

TH-302 50mg; doxorubicin 50mg

Drug: Phase I dose level 1

Phase I Dose level 2

EXPERIMENTAL

TH-302 100mg; doxorubicin 50mg

Drug: Phase I Dose level 2

Phase 1 Dose level 3

EXPERIMENTAL

TH-302 150mg; Doxorubicin 50mg

Drug: Phase I Dose level 3

Interventions

Phase I dose level 1 DRUG

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 2 DRUG

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 2

Phase I Dose level 3 DRUG

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

Phase 1 Dose level 3

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age
• Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
• Patients with hepatocellular carcinoma with either:
• liver limited disease who are not transplant candidates as they fall outside of Milan criteria, but may be eligible for transplant after successful downstaging with TACE
• liver limited disease who satisfy Milan criteria, but are at risk of falling out of Milan criteria before they receive a liver transplant
• non-transplantable HCC but with liver limited or metastatic disease that requires local TACE therapy
• Measurable disease by modified RECIST criteria (at least one target lesion outside of previous radiation fields)
• ECOG performance status of 2 or less
• Life expectancy of at least 3 months
• Childs-Pugh Class A or B
• HCC amenable to TACE
• Acceptable liver function:
• Bilirubin \< 2 mg/dL
• AST (SGOT) and ALT (SGPT) \< 5 x ULN is allowed
• Acceptable renal function:

You may not qualify if:

• New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, unstable arrhythmia or symptomatic peripheral arterial vascular disease
• Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for \>=3 months)
• Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancer from which the subject has been disease-free for at least 5 years
• Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation \<90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause systemic or regional hypoxemia
• Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Sorafenib within the previous 4 weeks or the intention to initiate sorafenib while on study
• Poor liver function as indicated by serum bilirubin \> 2 mg/dL, Child-Pugh Class C, severe coagulopathy (INR \> 2) not correctable with vitamin K, or active hepatic encephalopathy
• Main portal vein occlusion
• Liver rupture or tumor penetration of liver capsule
• Tumor invasion of biliary system with biliary obstruction
• Severe cytopenias, including ANC \< 500 cells/μL, Hemoglobin \< 8 g/dL, or platelets \< 50,000/μL
• Subjects who have exhibited allergic reactions to a structural compound, biological agent similar to TH-302
• Females who are pregnant or breast-feeding
• Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

Sponsors & Collaborators

• Scripps Clinic Cancer Center: lead
• Threshold Pharmaceuticals: collaborator

Study Sites (1)

Scripps Clinic

La Jolla, California, 92037, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Darren S Sigal, MD

  Scripps Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alain Perez

CONTACT

858-554-9379; Perez.Alain@scrippshealth.org

Study Design

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

Study Record Dates

• First Submitted: October 8, 2012
• First Posted: November 6, 2012
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: July 4, 2014

Record last verified: 2014-07

Locations

US (1)