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

Unknown

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

30

Phase

  • 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 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

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
Intervention / Treatment
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

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

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

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Collaborators

Sanofi
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Investigators

  • 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

September 1, 2013

Primary Completion (Anticipated)

June 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

March 24, 2015

First Submitted That Met QC Criteria

March 26, 2015

First Posted (Estimate)

March 31, 2015

Study Record Updates

Last Update Posted (Estimate)

January 5, 2016

Last Update Submitted That Met QC Criteria

January 4, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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