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

Carcinoma, Hepatocellular Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02403544
• Other study ID #: CH-GI-048
• Secondary ID: 13-102/778
• Status: Recruiting
• Phase: Phase 1
• First received: March 24, 2015
• Last updated: January 4, 2016
• Start date: September 2013
• Est. completion date: December 2016

Study information

• Verified date: January 2016
• Source: Chinese Academy of Medical Sciences
• Contact: Jing Jin, doctor
• Phone: 86-10-87787456
• Email: Jingjin1025[@]163.com
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Radiation:
• IGRT
IGRT: 45 to 54Gy, 1.8-3Gy per fraction.

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.
• Oxaliplatin
Oxaliplatin: intravenously, D1 and D8, every 21 days, 30mg/m2 per day in level 1, and then escalated every another dose level.

Locations

Country	Name	City	State
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (3)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences	Jiangsu Chia-tai Tianqing Pharmaceutical Co.,Ltd, Sanofi

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) for capecitabine and oxaliplatin		up to four weeks after the end of the treatment.	Yes
Secondary	Dose Limiting Toxicity (DLT)		up to four weeks after the end of the treatment.	Yes
Secondary	In field recurrence rate (LR) or local failure free survival (LFFS)		From the completion of CCRT to 6, 12, 24, 36 months afterward.	No
Secondary	Intrahepatic failure rate or intrahepatic failure free survival (IHFFS)		From the completion of CCRT to 6, 12, 24, 36 months afterward.	No
Secondary	Extrahepatic failure rate or extrahepatic failure free survival (EHFFS)		From the completion of CCRT to 6, 12, 24, 36 months afterward.	No
Secondary	Overall survival		From the completion of CCRT to 6, 12, 24, 36 months afterward.	No
Secondary	Tumor response rate including complete response and partial response rates		1 month and 3 month from the end of CCRT	No