Gemcitabine With Oxaliplatin (GEMOX) in Patients With Advanced Hepatocellular Carcinoma After Failure of Sorafenib Treatment (PEACH)

Phase II Study of Gemcitabine With Oxaliplatin in Patients With Advanced Hepatocellular Carcinoma After Failure of Sorafenib Treatment

The purpose of this study is to test the safety of gemcitabine and oxaliplatin regimen and to see its effects on sorafenib treatment failed hepatocellular carcinoma patients.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma, Unresectable, Advanced
• Intervention / Treatment: Drug: Gemcitabine, Oxaliplatin

Detailed Description

Patients who progressed after or cannot tolerate sorafenib treatment. Patients who cannot receive sorafenib for other reason are also permitted. Treatment is given in cycles, each cycle is 2 weeks long. Tumor measurements by CT and/or MRI will be repeated every 3 cycles. Patients will continue to receive study treatment as long as there is no disease progression or unacceptable side affects.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health system, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient who signed informed consent.
2. Male or female ≥ 20 years of age.
3. Diagnosis of advanced HCC according to the AASLD.
4. Unresectable HCC
5. Advanced disease defined as extrahepatic metastasis or locally advanced disease not amenable to surgical resection or other local-regional therapies including transhepatic arterial (chemo) embolization (TACE or TAE) and local ablative therapy
6. Patient who progressed after prior local-regional therapy (local-regional therapy must be completed at least 4weeks prior to the baseline).

7. Patients who progressed after or cannot tolerate sorafenib treatment. Patients who cannot receive sorafenib for other reason are also permitted.

   • Documented radiological confirmation of disease progression during or after sorafenib treatment
   • Intolerance to sorafenib is defined as documented sorafenib-related grade 3 or 4 adverse events that led to sorafenib discontinuation
8. Patients must have a life expectancy of at least 12 weeks.
9. Eastern Cooperative Oncology Group (ECOG) performance state ≤ 2
10. Measurable lesion according to the RECIST 1.1 criteria
11. Child Pugh Class A or B7

12. Patients must have adequate organ and marrow function:

    • Absolute neutrophil count (ANC) ≥1.5X10^9/L
    • Platelets≥75X10^9/L
    • Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) < 5 Upper Normal Limit(UNL)
    • Total Bilirubin≤1.5 X UNL
13. Controlled brain metastasis is allowed(except brain metastasis to require treatment to control symptom-wash out of treatment for brain metastasis is not required.)

Exclusion Criteria:

1. Imaging findings for HCC corresponding to any of the following

   • HCC with >60% liver occupation
   • Portal vein invasion at the main portal branch (Vp4)

2. History of a secondary malignancy within 3 years

   - in situ cervical cancer, adequately treated basal cell or superficial bladder cancer

3. History of chemotherapy or radiotherapy within 4 weeks

   - but, 2 weeks for sorafenib and radiotherapy site of bone lesion

4. Patient who not recovered toxicity ≥ grade 2 related prior local-regional therapy or systemic therapy.
5. Patients with any known severe allergy to Gemcitabine or platinum compound.
6. Active gastro-Intestinal bleeding.
7. Patients who are receiving any other chemotherapy or study treatments.
8. Pregnant or lactating women or women of childbearing potential without proper contraceptive methods.
9. Patients with active infections requiring an IV antibiotic.
10. Neuropathy ≥ grade 2
11. Patients with known interstitial lung disease or pulmonary fibrosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine, Oxaliplatin; Gemcitabine 1,000 mg/m2 infusion for 30minutes and followed by oxaliplatin 100mg/m2 infusion for 2hours on day1. All drugs were administered intravenously until progression, intolerance, patient withdrawal, or death.	Drug: Gemcitabine, Oxaliplatin; Gemcitabine 1,000 mg/m2 infusion for 30minutes and followed by oxaliplatin 100mg/m2 infusion for 2hours on day1. All drugs were administered intravenously until progression, intolerance, patient withdrawal, or death.; Other Names: Gemzar, Eloxatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Overall safety profile verified as relevance of adverse events and laboratory abnormality based on CTCAE v4.0.	From enrollment to 30 days follow-up after the end of treatment
Response rate	Assessed by RECIST 1.1	from enrollment to 1 year follow-up after the end of treatment
Overall survival	Estimated by the Kaplan-Meier method	From enrollment to 1 year follow-up after the end of treatment

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Hye Jin Choi, Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): September 30, 2019
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): August 26, 2022
• Last Update Submitted That Met QC Criteria: August 25, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine; Oxaliplatin
• Other Study ID Numbers: 4-2014-0269

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No