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

NCT02403544 | Unknown Phase 1 DMC

• 2 other identifiers: CH-GI-04813-102/778
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Carcinoma, Hepatocellular

Keywords

Clinical Trial, Phase I; Concurrent Chemoradiation; Oxaliplatin; Capecitabine; Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) for capecitabine and oxaliplatin

  up to four weeks after the end of the treatment.

Secondary Outcomes (6)

• Dose Limiting Toxicity (DLT)

  up to four weeks after the end of the treatment.

• In field recurrence rate (LR) or local failure free survival (LFFS)

  From the completion of CCRT to 6, 12, 24, 36 months afterward.

• Intrahepatic failure rate or intrahepatic failure free survival (IHFFS)

  From the completion of CCRT to 6, 12, 24, 36 months afterward.

• Extrahepatic failure rate or extrahepatic failure free survival (EHFFS)

  From the completion of CCRT to 6, 12, 24, 36 months afterward.

• Overall survival

  From the completion of CCRT to 6, 12, 24, 36 months afterward.

Study Arms (1)

CCRT Arm

EXPERIMENTAL

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; Drug: Capecitabine; Drug: Oxaliplatin

Interventions

IGRT RADIATION

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

Also known as: Image-guided radiation therapy

CCRT Arm

Capecitabine DRUG

Capecitabine: by oral, D1-14, every 21 days, 600mg/m2 bid per day in level 1, and then escalated every another dose level.

Also known as: CCRT concurrent chemotherapy 1 capecitabine

CCRT Arm

Oxaliplatin DRUG

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

Also known as: CCRT concurrent chemotherapy 2 oxaliplatin

CCRT Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator
• Sanofi: collaborator

Study Sites (1)

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiotherapy, Image-Guided; Capecitabine; Oxaliplatin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Officials

• Jing Jin, doctor

  Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

Jing Jin, doctor

CONTACT

86-10-87787456; Jingjin1025@163.com

Hao Jing, doctor

CONTACT

86-10-87788122; owletskim@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair of Department of Radiation Oncology, Cancer Hospital

Study Record Dates

• First Submitted: March 24, 2015
• First Posted: March 31, 2015
• Study Start: September 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 5, 2016

Record last verified: 2016-01

Locations

CN (1)