Phase I Study of Image-Guided Radiation Concurrent With Double-Agent Chemotherapy for Hepatocellular Carcinoma

January 4, 2016 updated by: Jing Jin, M.D., Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Image-Guided Radiation Therapy (IGRT) Associated With Concurrent Capecitabine and Oxaliplatin in the Treatment of Locally Advanced or Inoperable Hepatocellular Carcinoma (HCC): A Phase I Study

This is a phase I study to evaluate the safety of concurrent chemoradiation combining radiotherapy (IGRT) with two cytotoxic agents, capecitabine and oxaliplatin in patients with advanced or inoperable hepatocellular carcinoma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In this phase I study, patients with advanced or inoperable hepatocellular carcinoma, or those failed other strategies will be recruited. The primary tumor and nearby metastatic nodes will be irradiated with Image-Guided Radiation Therapy (IGRT) mostly with conventional fractions. During the course, oral capecitabine and intravenous oxaliplatin will be given concurrently. The maximum tolerated dose (MTD) for the two drugs will be determined during escalation according to the occurrence of dose limiting toxicities (DLT).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100021
        • Recruiting
        • Cancer Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Criteria:

Inclusion Criteria:

  • KPS≥80.
  • Life expectancy≥16 months.
  • Histopathologically or clinically diagnosed HCC.
  • Barcelona-Clinic Liver Cancer (BCLC) 0-C without distant metastasis.
  • The primary tumor is unresectable, inoperable or failed in other previous therapies.
  • Child-pugh≤6 (Child A), Indocyanine green retention rate at 15min <20%.
  • HGb≥100g/L, WBC≥3×109/L, NEUT≥1.5×109/L, PLT≥75×109/L, Creatine≤1.5mg/dl (UNL), Bun≤30mg/dl, Alanine aminotransferase/Aspartate aminotransferase/Alkaline phosphatase≤2.5×UNL, TBil≤1.5×UNL, Prothrombin time≤1.5×UNL, INR≤1.5.
  • No prior liver or upper abdomen radiation therapy.
  • No previous history of allergic reaction attributed to fluorouracil or platinum drugs.
  • Be conscious and could cooperate and comply with protocols for the study, such as simulation, smooth breathing and positioning for radiotherapy.
  • Be ready to be followed up.
  • Fulfill dosages requirement for targets and dose limits for organs at risk.
  • The patient should be under anti-hepatitis-virus therapy if indicated.
  • Sorafenib should be discontinued 7 days before the start of irradiation.
  • Subjects informed of the diagnosis of advanced HCC who are fully informed about the content of the study by the investigator using the written consent form, and give written consent to participate in the study of their own free will.

Exclusion Criteria:

  • KPS≤70.
  • Existing distant metastasis.
  • Child-Pugh≥7, Indocyanine green retention rate at 15min ≥20%.
  • Primary tumor within the liver is not to be irradiated.
  • Past liver transplantation.
  • Complications of cirrhosis: active gastrointestinal bleeding, hepatic encephalopathy, refractory ascites, peritonitis, hepatorenal syndrome, hepatopulmonary syndrome.
  • Upper gastrointestinal bleeding within 3 months.
  • Any other carcinomas, except cured non-melanoma skin carcinoma, treated in-situ cervical cancer and ≤T1 bladder cancer.
  • After planning optimization, the physician still consider risky to treat the patient with the plan or the benefit is negligible.
  • Not conscious or can not cooperate or comply with the protocol for the study.
  • Previous history of allergic reaction attributed to fluorouracil or platinum.
  • Patients with serious comorbidities or uncontrolled medical conditions that the investigator feels might compromise study participation (including but not limited to: myocardial infarction, congestive heart failure (NYHA>2), unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled psychotic disorders, uncontrolled hypertension and cerebrovascular disease with previous stroke within 6 months, serious infections，positive HIV test, poorly controlled diabetes mellitus with fasting blood-glucose >8mmol/L or 2-hour postprandial blood glucose >11mmol/L within the past month).
  • Thrombolytic therapy within 4 weeks, or any concurrent anti-coagulant therapy.
  • Pregnant, nursing, or possibly pregnant women, or women desiring to become pregnant during the study period.
  • Participation in any investigational study within 4 weeks preceding the start of study treatment.
  • Other cases judged by the investigator to be ineligible for participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CCRT Arm
Patients recruited will be treated by concurrent chemoradiotherapy with IGRT and two cytotoxic agents: capecitabine and oxaliplatin. Capecitabine will be taken orally twice a day, from D1 to D14 while oxaliplatin will be given intravenously on D1 and D8, every 21 days. The doses of the two drugs will be escalated alternatively in each level group. The radiation will be given by IGRT and the dose is between 45 to 54Gy, 1.8-3Gy per fraction.
Radiation: IGRT
IGRT: 45 to 54Gy, 1.8-3Gy per fraction.
Other Names:
  • Image-guided radiation therapy
Drug: Capecitabine
Capecitabine: by oral, D1-14, every 21 days, 600mg/m2 bid per day in level 1, and then escalated every another dose level.
Other Names:
  • CCRT concurrent chemotherapy 1 capecitabine
Drug: Oxaliplatin
Oxaliplatin: intravenously, D1 and D8, every 21 days, 30mg/m2 per day in level 1, and then escalated every another dose level.
Other Names:
  • CCRT concurrent chemotherapy 2 oxaliplatin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Maximum Tolerated Dose (MTD) for capecitabine and oxaliplatin
Time Frame: up to four weeks after the end of the treatment.
up to four weeks after the end of the treatment.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Dose Limiting Toxicity (DLT)
Time Frame: up to four weeks after the end of the treatment.
up to four weeks after the end of the treatment.
In field recurrence rate (LR) or local failure free survival (LFFS)
Time Frame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
From the completion of CCRT to 6, 12, 24, 36 months afterward.
Intrahepatic failure rate or intrahepatic failure free survival (IHFFS)
Time Frame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
From the completion of CCRT to 6, 12, 24, 36 months afterward.
Extrahepatic failure rate or extrahepatic failure free survival (EHFFS)
Time Frame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
From the completion of CCRT to 6, 12, 24, 36 months afterward.
Overall survival
Time Frame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
From the completion of CCRT to 6, 12, 24, 36 months afterward.
Tumor response rate including complete response and partial response rates
Time Frame: 1 month and 3 month from the end of CCRT
1 month and 3 month from the end of CCRT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Sanofi
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Jing Jin, doctor, Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2013

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2016

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 24, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 31, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 5, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CH-GI-048
  • 13-102/778 (Other Identifier: Ethics Committee of Cancer Institute and Hospital)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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