Clinical trial NCT02403544: Phase I Study of Image-Guided Radiation Concurrent With Double-Agent Chemotherapy for Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Carcinoma, Hepatocellular
Keywords: Clinical Trial, Phase I
Concurrent Chemoradiation
Oxaliplatin
Capecitabine
Carcinoma, Hepatocellular
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
Collaborators: name: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
name: Sanofi
First posted: 2015-03-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) for capecitabine and oxaliplatin
timeFrame: up to four weeks after the end of the treatment.
Secondary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: up to four weeks after the end of the treatment.
measure: In field recurrence rate (LR) or local failure free survival (LFFS)
timeFrame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
measure: Intrahepatic failure rate or intrahepatic failure free survival (IHFFS)
timeFrame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
measure: Extrahepatic failure rate or extrahepatic failure free survival (EHFFS)
timeFrame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
measure: Overall survival
timeFrame: From the completion of CCRT to 6, 12, 24, 36 months afterward.
measure: Tumor response rate including complete response and partial response rates
timeFrame: 1 month and 3 month from the end of CCRT
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences
name: Jing Jin, doctor
role: STUDY_DIRECTOR
References: