Hepatocellular CarcinomaPhase 1NCT01721941
TH-302 Plus Doxorubicin Delivered by Trans-Arterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma
A Phase 1 study testing Phase I Dose level -1, Phase I dose level 1 and Phase I Dose level 2 in people with Hepatocellular Carcinoma, run by Scripps Clinic Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Phase I Dose level -1, Phase I dose level 1 and Phase I Dose level 2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Patent main portal vein (thrombosis of portal vein branch not exclusionary)
- Acceptable liver function:
- Bilirubin < 2 mg/dL
- AST (SGOT) and ALT (SGPT) < 5 x ULN is allowed
- Acceptable renal function:
- Serum creatinine < 1.5 ULN
- Acceptable hematologic status (without hematologic support for TACE #1):
- ANC > 500 cells/μL
- Platelet count > 50,000/μL
Who cannot join
- 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
Show all 16Show fewer
- 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
- Unwillingness or inability to comply with the study protocol for any reason
Trial locations and contacts
1 site in 1 country.
United States1 site
Scripps Clinic
La Jolla, California, 92037
Alain Perez, 858-554-8937, Perez.Alain@scrippshealth.org
Darren S Sigal, M.D.
About this study
Official title: A Phase I Dose Escalation Study of TH-302 Plus Doxorubicin Delivered by Trans-Arterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma
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.
Read the detailed description
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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Phase I Dose level -1, Phase I dose level 1, Phase I Dose level 2, Phase I Dose level 3
- Keywords
- hepatocellular carcinoma, HCC, liver cancer, hepatoma, TACE, transarterial chemoembolization, TH302
- Medical subject headings
- Carcinoma, Hepatocellular, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phase I Dose level -1Drug
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 1Drug
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 2Drug
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 3Drug
The dose of TH-302 will be mixed with doxorubicin 50mg to use as the chemoembolization mixture for transarterial chemoembolization (TACE).
| Study group | Role | What they receive |
|---|---|---|
| Phase I dose level -1 | Experimental | TH-302 25mg; Doxorubicin 50mg Receives: Drug: Phase I Dose level -1 |
| Phase I Dose level 1 | Experimental | TH-302 50mg; doxorubicin 50mg Receives: Drug: Phase I dose level 1 |
| Phase I Dose level 2 | Experimental | TH-302 100mg; doxorubicin 50mg Receives: Drug: Phase I Dose level 2 |
| Phase 1 Dose level 3 | Experimental | TH-302 150mg; Doxorubicin 50mg Receives: Drug: Phase I Dose level 3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 33 weeks
Secondary outcomes (1)
Objective response rate
Assess overall response rate using standard RECIST criteria measured by triple phase CT or MRI at least 6 weeks post TACE administration
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2012 (estimated)
- Study startDec 2014
- Primary completionDec 2015 (estimated)
- Study completionDec 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Scripps Clinic Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Threshold Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Darren S Sigal, MD, Principal investigator, Scripps Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01721941
- Sponsor's protocol ID
- TH302 TACE
- Status last verified
- Jul 2014
- First submitted
- 8 Oct 2012
- Last updated
- 4 Jul 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of TH-302 Plus Doxorubicin Delivered by Trans-Arterial Chemoembolization (TACE) in Patients With Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT01721941
- Acronym / sponsor ID
- TH302 TACE
- Conditions
- Hepatocellular Carcinoma
- Keywords
- hepatocellular carcinoma, HCC, liver cancer, hepatoma, TACE, transarterial chemoembolization, TH302
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Scripps Clinic Cancer CenterUniversity, hospital or other
- Collaborators
- Threshold Pharmaceuticals
- Study start
- Dec 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Dec 2016 (estimated)
- First posted
- 6 Nov 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase I dose level -1 | Experimental | Drug: Phase I Dose level -1TH-302 25mg; Doxorubicin 50mg |
| Phase I Dose level 1 | Experimental | Drug: Phase I dose level 1TH-302 50mg; doxorubicin 50mg |
| Phase I Dose level 2 | Experimental | Drug: Phase I Dose level 2TH-302 100mg; doxorubicin 50mg |
| Phase 1 Dose level 3 | Experimental | Drug: Phase I Dose level 3TH-302 150mg; Doxorubicin 50mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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:
- Measurable disease by modified RECIST criteria (at least one target lesion outside of previous radiation fields)
- ECOG performance status of 2 or less
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phase I Dose level -1The dose of TH-302 will be mixed with doxorubicin 50mg to use as the chemoembolization mixture for transarterial chemoembolization (TACE). | Drug | Phase I dose level -1 |
| Phase I dose level 1The dose of TH-302 will be mixed with doxorubicin 50mg to use as the chemoembolization mixture for transarterial chemoembolization (TACE). | Drug | Phase I Dose level 1 |
| Phase I Dose level 2The dose of TH-302 will be mixed with doxorubicin 50mg to use as the chemoembolization mixture for transarterial chemoembolization (TACE). | Drug | Phase I Dose level 2 |
| Phase I Dose level 3The dose of TH-302 will be mixed with doxorubicin 50mg to use as the chemoembolization mixture for transarterial chemoembolization (TACE). | Drug | Phase 1 Dose level 3 |
Primary outcome
Maximum tolerated dose of TH-302 use in TACE
Time frame: 33 weeks
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.
1 secondary outcome
Objective response rate
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jul 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Darren S Sigal, MD principal investigator
Scripps Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Phase I Dose level -1, Phase I dose level 1 and Phase I Dose level 2 in people with Hepatocellular Carcinoma, run by Scripps Clinic Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alain Perez (858-554-9379, Perez.Alain@scrippshealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose of TH-302 use in TACE (time frame: 33 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jul 2014.