Liver Cancer
Conditions
Keywords
advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer, adult primary hepatocellular carcinoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving chemotherapy together with a monoclonal antibody may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving oxaliplatin and capecitabine together with cetuximab works in treating patients with advanced liver cancer.
Detailed description
OBJECTIVES: Primary * Determine the response rate in patients with advanced hepatocellular carcinoma and hepatic dysfunction treated with oxaliplatin, capecitabine, and cetuximab. Secondary * Determine the safety of this regimen in these patients. * Determine the overall survival of patients treated with this regimen. * Determine the time to tumor progression in patients treated with this regimen. OUTLINE: This is an open label, nonrandomized study. Patients receive oral capecitabine twice daily on days 1-14, cetuximab IV over 60-120 minutes on days 1, 8, and 15, and oxaliplatin IV over 120 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 3-4 weeks and then every 3 months thereafter.
Interventions
BIOLOGICALcetuximab
250 mg/m2, intravenously, once per week
DRUGcapecitabine
850 mg/m2, orally, twice daily (dose rounded to accommodate 150 mg and 500 mg tablet sizes. Capecitabine given on days 1-14 of 21 day cycle.
DRUGoxaliplatin
130 mg/m2, intravenously on Day 1 of each 21 day cycle
Sponsors
Sanofi
Roche Pharma AG
Bristol-Myers Squibb
National Center for Research Resources (NCRR)
National Cancer Institute (NCI)
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Meets 1 of the following criteria: * Histologically confirmed hepatocellular carcinoma * Alpha-fetoprotein (AFP) \> 400 ng/mL with compatible mass by CT scan or MRI * Metastatic disease OR not a candidate for surgical resection or immediate liver transplantation * At least 1 site of measurable disease OR evaluable disease (AFP 2 times upper limit of normal (ULN)) * No evidence of central nervous system (CNS) metastases (unless CNS metastases stable for \> 3 months) PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Absolute neutrophil count (ANC) ≥ 1,500/mm³ * Hemoglobin ≥ 9 g/dL * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 3 times ULN * International normalized ratio (INR) ≤ 1.5 * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 times ULN * Creatinine clearance \> 50 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No known hypersensitivity to capecitabine, cetuximab, or oxaliplatin or to other murine products * No comorbid condition which is deemed by the investigator to have a life expectancy of \< 6 months * No New York Heart Association class III-IV coronary artery disease and/or heart failure * No variceal bleeding within the past 60 days * No other cancer within the past 5 years except cervical intraepithelial neoplasia, nonmelanoma skin cancer, ductal carcinoma in situ, chronic lymphocytic leukemia, or treated localized prostate cancer with a normal prostate specific antigen level * No active drug or alcohol abuse * No prior allergic reaction to a therapeutic antibody * No serious, uncontrolled infection * No history of uncontrolled seizures, CNS disorders, or psychiatric disability that, in the opinion of the investigator, would preclude study participation or compliance * No other serious uncontrolled medical condition that, in the opinion of the investigator, would preclude study participation * No lack of physical integrity of the upper gastrointestinal tract * No malabsorption syndrome * No known existing uncontrolled coagulopathy PRIOR CONCURRENT THERAPY: * At least 4 weeks since prior participation in an investigational drug trial * At least 4 weeks since prior major surgery and recovered * At least 4 weeks since prior embolization, resection, or ablation * No prior epidermal growth factor receptor (EGFR)-targeting therapy * No prior systemic chemotherapy or hepatic artery infusion of chemotherapy * No concurrent phenytoin * No concurrent therapeutic warfarin * Low-dose non-therapeutic warfarin to maintain patency of venous access devices allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Response Rate | 42 days (2 cycles) | Radiographic response will be measured every six weeks while subject is on treatment. Response will be measured using RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Experiencing Adverse Events | every 3 weeks of treatment with an average of 15 weeks on treatment | Adverse events will be assessed using CTCAE criteria. |
| Overall Survival | Median 23 month follow-up | Overall survival will be calculated from time of enrollment to death or last contact date. |
| Time to Progression | Median 23 month follow-up | Time to progression will be calculated from the time of enrollment until confirmed disease progression. Defined by RECIST (Response Evaluation Criteria in Solid Tumors), Progressive Disease (PD) - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. |
Countries
United States
Participant flow
Pre-assignment details
Of the 33 enrolled; 2 patients withdrew or refused prior to the beginning of protocol therapy, 2 patients were found to be ineligible, and 1 patient was withdrawn when diagnosis changed to sarcoma.
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Trial Single Arm Trial
cetuximab: 250 mg/m2, intravenously, once per week
capecitabine: 850 mg/m2, orally, twice daily (dose rounded to accommodate 150 mg and 500 mg tablet sizes. Capecitabine given on days 1-14 of 21 day cycle.
oxaliplatin: 130 mg/m2, intravenously on Day 1 of each 21 day cycle | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Death | 3 |
| Overall Study | Lack of Efficacy | 14 |
| Overall Study | Other complicating disease | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Single Arm Trial |
|---|---|
| Age, Continuous | 59 years |
| Childs-Pugh Classification Class A (5-6 points) | 18 Participants |
| Childs-Pugh Classification Class B (7-9 points) | 6 Participants |
| Childs-Pugh Classification Class C (10-15 points) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Prior Therapy None | 15 Participants |
| Prior Therapy Yes | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 23 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 14 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 12 Participants |
| The Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 27 / 29 |
| other Total, other adverse events | 27 / 29 |
| serious Total, serious adverse events | 17 / 29 |
Outcome results
Primary
Disease Response Rate
Radiographic response will be measured every six weeks while subject is on treatment. Response will be measured using RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: 42 days (2 cycles)
Population: Four patients received some protocol treatment but withdrew before completing one cycle without assessment of response.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Arm Trial | Disease Response Rate | 12.5 percentage of participants with response |
Secondary
Number of Subjects Experiencing Adverse Events
Adverse events will be assessed using CTCAE criteria.
Time frame: every 3 weeks of treatment with an average of 15 weeks on treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single Arm Trial | Number of Subjects Experiencing Adverse Events | 29 Participants |
Secondary
Overall Survival
Overall survival will be calculated from time of enrollment to death or last contact date.
Time frame: Median 23 month follow-up
Population: Four patients received some protocol treatment but withdrew before completing one cycle without assessment of response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Arm Trial | Overall Survival | 4.4 months |
Secondary
Time to Progression
Time to progression will be calculated from the time of enrollment until confirmed disease progression. Defined by RECIST (Response Evaluation Criteria in Solid Tumors), Progressive Disease (PD) - at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Median 23 month follow-up
Population: Four patients received some protocol treatment but withdrew before completing one cycle without assessment of response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Arm Trial | Time to Progression | 4.5 months |