Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
Conditions
Brief summary
This phase II trial is studying how well IMC-A12 works in treating patients with advanced liver cancer. Monoclonal antibodies, such as IMC-A12, 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.
Detailed description
PRIMARY OBJECTIVES: I. To determine the progression-free survival (PFS) at 4 months in patients with advanced hepatocellular carcinoma (HCC) treated with anti-IGF-1R recombinant monoclonal antibody IMC-A12. II. To determine the best overall response rate in patients treated with this drug. SECONDARY OBJECTIVES: I. To determine the median overall survival of patients treated with this drug. II. To evaluate the safety, tolerability, and adverse events profile of this drug in these patients. III. To perform a subgroup analysis to compare PFS of patients with advanced HCC who are hepatitis B positive/hepatitis C negative versus patients who are hepatitis B negative/hepatitis C positive treated with this drug. IV. To store pre-therapy paraffin embedded tumor tissue for future tissue-based correlative studies. V. To evaluate tumor necrotic areas using a new volumetric method of assessing non-viable tumor as a correlate for response. VI. To prospectively validate and compare the CLIP and the GDETCH staging systems and additional prognostic factors. OUTLINE: Patients receive anti-IGF-1R recombinant monoclonal antibody IMC-A12 IV over 1 hour once weekly. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo serum sample collection at baseline for future tissue-based correlative studies. Previously collected paraffin embedded tumor tissue samples are also stored for future correlative studies. After completion of study treatment, patients are followed every 3 months for at least 1 year.
Interventions
BIOLOGICALcixutumumab
Given IV
PROCEDUREcomputed tomography
Undergo contrast-enhanced computed tomography
Undergo contrast-enhanced magnetic resonance imaging
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed hepatocellular carcinoma * Unresectable, locally advanced, or metastatic disease * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan * Child's Pugh score A5, A6, B7, or B8 * No known brain metastases * No history of primary CNS tumors * ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% * Life expectancy \> 3 months * Leukocytes ≥ 3,000/mcL * Absolute neutrophil count ≥ 1,500/mcL * Platelet count ≥ 75,000/mcL * Total bilirubin ≤ 2 times upper limit of normal (ULN) * AST/ALT ≤ 2.5 times ULN * PT/INR ≤ 1.7 times ULN * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min * Fasting serum glucose ≤ 125 mg/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No clinical encephalopathy * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12 * No poorly controlled diabetes mellitus * Patients with a history of diabetes mellitus are eligible provided their blood glucose is within normal range (fasting blood glucose \< 120 mg/dL OR below ULN) and patient is on a stable dietary or therapeutic regimen for this condition * No concurrent uncontrolled illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness or social situation that would preclude compliance with study requirements * No history of seizures not well controlled with standard medical therapy * No history of stroke * No history of another primary cancer except for the following: * Curatively resected nonmelanoma skin cancer * Curatively treated carcinoma in situ of the cervix * Other primary solid tumor with no known active disease present that in the opinion of the investigator would not affect treatment outcome * Prior local therapy (i.e., surgery, radiotherapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) allowed provided the target lesion has not been treated with local therapy and/or the target lesion within the field of local therapy has shown an increase of ≥ 25% in size * At least 4 weeks since prior local therapy * No prior systemic therapy except for sorafenib tosylate * No prior agents targeting the IGF or IGF-1R pathway * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS Rate | At 4 months | PFS defined as the time from first date of first treatment on the study until such time as progressive disease is confirmed or upon patient death if disease progression has not been evident at that time. A Simon's optimal two stage design will be used with the following assumption: a 4 months PFS of 62% is considered acceptable while a 4 months PFS of 42% is not acceptable. |
| Best Overall Response Rate (ORR) | From the start of the treatment until disease progression/recurrence | Best overall ORR will be defined as the proportion of patients achieving either confirmed partial response (PR) or confirmed complete response (CR). A Simon's optimal two stage design will be used with the following assumption: ORR of more than 20% is acceptable and an ORR less than 5% is not acceptable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | Post-Treatment | Median Overall Survival |
Countries
United States
Participant flow
Recruitment details
Protocol Open to Accrual 03/06/2008 Primary Completion Date 02/08/2011 Recruitment Location is medical clinic
Participants by arm
| Arm | Count |
|---|---|
| IMC-A12 Participants will receive IMC-A12 at a dose of 6mg/kg IV over 1 hour on Day 1 every week. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | IMC-A12 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 67.5 years STANDARD_DEVIATION 9.469631093 |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 24 |
| serious Total, serious adverse events | 11 / 24 |
Outcome results
Primary
Best Overall Response Rate (ORR)
Best overall ORR will be defined as the proportion of patients achieving either confirmed partial response (PR) or confirmed complete response (CR). A Simon's optimal two stage design will be used with the following assumption: ORR of more than 20% is acceptable and an ORR less than 5% is not acceptable.
Time frame: From the start of the treatment until disease progression/recurrence
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Monoclonal Antibody Therapy) | Best Overall Response Rate (ORR) | 0 participants |
Primary
PFS Rate
PFS defined as the time from first date of first treatment on the study until such time as progressive disease is confirmed or upon patient death if disease progression has not been evident at that time. A Simon's optimal two stage design will be used with the following assumption: a 4 months PFS of 62% is considered acceptable while a 4 months PFS of 42% is not acceptable.
Time frame: At 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Monoclonal Antibody Therapy) | PFS Rate | 30 percentage of participants |
Secondary
Median Overall Survival
Median Overall Survival
Time frame: Post-Treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Monoclonal Antibody Therapy) | Median Overall Survival | 8 months |