Oxaliplatin and Capecitabine on Top of Sorafenib Versus Sorafenib Alone in Advanced Hepatocellular Carcinoma Patients (SECOX)

A Randomized Phase III Study of Oxaliplatin (Eloxatin) and Capecitabine on Top of Sorafenib Versus Sorafenib Alone as First-line Palliative Treatment in Advanced Hepatocellular Carcinoma Patients

Primary Objective:

- To evaluate the efficacy of SECOX regimen by adding oxaliplatin plus capecitabine to sorafenib versus sorafenib alone as palliative treatment for unresectable HCC patients to prolong overall survival (OS) for advanced HCC patients.

Secondary Objective:

• To compare the efficacy of SECOX regimen with Sorafenib alone for progression free survival (PFS)
• To compare the efficacy of SECOX regimen with Sorafenib alone for response rate (RR)
• To assess the overall safety profile of SECOX regimen in comparison of Sorafenib alone

Study Overview

• Status: Withdrawn
• Conditions: Hepatic Neoplasm Malignant
• Intervention / Treatment: Drug: oxaliplatin (SR96669); Drug: capecitabine; Drug: sorafenib

Detailed Description

For each patient, the study consists of a baseline period of screening up to 2 weeks, a treatment period with 2 weeks as one study treatment cycle.

Each patient will be randomly assigned to receive either SECOX (Sorafenib, Oxaliplatin with Capecitabine) or Sorafenib alone every 2 weeks until disease progression, intolerable toxicity, or patient's refusal of further study treatment. There will be a 30-day follow-up visit after the last study treatment.

All patients will be follow-up every 2 months until death is observed during post-treatment follow-up period.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects with histologically or cytologically or clinically diagnosed advanced HCC not amenable to surgical or local treatment. Documentation of original pathology for diagnosis is acceptable if tumor tissue is unavailable at screening.
• Signed written informed consent

Exclusion criteria:

• Clinically diagnosed subjects who did not meet two following criteria:

  • cirrhotic patients with focal lesion > 2cm with arterial hypervascularization demonstrated by 2 coincident imaging techniques
  • cirrhotic patients with focal lesion > 2cm with arterial hypervascularization demonstrated by 1 imaging technique and associated with Alpha Fetoprotein (AFP) level > 400 ng/mL
• Subjects who are receiving or previously received any other investigational therapy or any other systemic anti-cancer treatment for HCC including chemotherapy, immunotherapy or targeted agents, except radiotherapy to non-target lesion (bone metastasis, etc) and HCC adjuvant therapy which was completed more than 6 months prior to randomization. Antiviral treatment is allowed, however interferon therapy must be stopped at least 4 weeks prior to randomization.
• Subjects with main portal vein thrombosis.
• Subjects with encephalopathy or history of encephalopathy, ascites uncontrolled by medication, active or history of variceal or gastrointestinal bleeding within 30 days
• Subjects with Central Nervous System (CNS) metastasis
• Subjects without one target tumor lesion that be measurable at baseline according to Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria
• Subjects who have received local therapy such as surgery, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection within 4 weeks prior to randomization
• Subjects with Child-Pugh > A
• Eastern Cooperative Oncology Group (ECOG) > 2
• Subjects with inadequate bone marrow, liver and renal function
• Subjects with previous liver transplantation
• Subjects with other serious diseases or medical conditions within 6 months that might be associated with a life expectancy of less than 3 months
• Subjects with other malignant disease previously or concurrently, except cured basal cell carcinoma of skin, cervical carcinoma in situ or any cancer curatively treated > 3 years prior to study entry
• Subjects with known severe hypersensitivity to sorafenib or any other component of sorafenib
• Pregnant or lactating women, or women of child bearing potential without contraceptive method or unwilling to take effective contraception during the study

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SECOX regimen; Oxaliplatin (Eloxatin) 85mg/m2 , 2 hour infusion, day 1 Capecitabine (Xeloda) 850 mg/m2 BID orally daily, from day 1 to 7 Sorafenib (Nexavar) 400 mg BID orally daily, from day 1 to 14 (continuously)	Drug: oxaliplatin (SR96669); Pharmaceutical form:injection Route of administration: intravenous; Drug: capecitabine; Pharmaceutical form:tablet Route of administration: oral; Drug: sorafenib; Pharmaceutical form:tablet Route of administration: oral
Active Comparator: Sorafenib alone; Sorafenib (Nexavar) 400 mg BID orally daily, from day 1 to 14 (continuously)	Drug: sorafenib; Pharmaceutical form:tablet Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	defined as the time from randomization to the date of death due to any cause. If death is not observed at the cut off date, data on OS will be censored at the last date when patient is known to be alive or the cut-off date, whichever comes first.	From the date of randomization to the date of death due to any cause.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	defined as the time interval from the date of randomization to the date of first observation of disease progression or the date of death (due to any cause). If death or progression is not observed, data on PFS will be censored at the earlier date of last tumor assessment without evidence of progression and the cut-off date.	From the date of randomization to the date of documentation of progression or death.
Response Rate (RR)	defined as the proportion of patients with confirmed complete response (CR) or confirmed partial response (PR), defined by RECIST 1.1 criteria	From the date of randomization to the end of study.

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Anticipated): February 1, 2014
• Study Completion (Anticipated): August 1, 2015

Study Registration Dates

• First Submitted: November 19, 2010
• First Submitted That Met QC Criteria: November 19, 2010
• First Posted (Estimate): November 22, 2010

Study Record Updates

• Last Update Posted (Estimate): November 9, 2011
• Last Update Submitted That Met QC Criteria: November 8, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Neoplasms; Carcinoma, Hepatocellular; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib; Capecitabine; Oxaliplatin
• Other Study ID Numbers: EFC11719; U1111-1115-8557 (Other Identifier: UTN); OXALI_R_05123 (Other Identifier: sanofi-aventis other reference)