IMC-A12 in Treating Patients With Advanced Liver Cancer
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Adult Primary Hepatocellular Carcinoma Advanced Adult Primary Liver Cancer Localized Unresectable Adult Primary Liver Cancer Recurrent Adult Primary Liver Cancer |
Biological: cixutumumab Procedure: computed tomography Procedure: contrast-enhanced magnetic resonance imaging |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 2 Study of IMC-A12 (NSC742460) in Hepatocellular Carcinoma |
- PFS rate [ Time Frame: At 4 months ] [ Designated as safety issue: No ]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) [ Time Frame: From the start of the treatment until disease progression/recurrence ] [ Designated as safety issue: No ]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.
- Overall survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier methodology.
- Median survival [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Estimated using the Kaplan-Meier methodology.
- The safety and tolerability of IMC-A12 monotherapy [ Time Frame: From the time of first treatment with IMC-A12, assessed up to 1 year ] [ Designated as safety issue: Yes ]Summarized using descriptive statistics.
- Adverse events profile of as assessed by the National Cancer Institute Common Terminology Criteria version 3.0 [ Time Frame: From time to first treatment to up to 1 year ] [ Designated as safety issue: Yes ]Summarized using descriptive statistics.
- Differences in the PFS of patients who are hepatitis B positive/hepatitis C negative versus patients who are hepatitis B negative/hepatitis C positive [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]Tested using the log-rank test
- Ability of the volumetric method to assess response to treatment compared to standard Response Evaluation Criteria in Solid Tumors (RECIST) criteria [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]McNemar's test will be used.
| Enrollment: | 50 |
| Study Start Date: | March 2008 |
| Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (monoclonal antibody therapy)
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.
|
Biological: cixutumumab
Given IV
Other Names:
Procedure: computed tomography
Undergo contrast-enhanced computed tomography
Other Name: tomography, computed
Procedure: contrast-enhanced magnetic resonance imaging
Undergo contrast-enhanced magnetic resonance imaging
Other Name: Contrast-enhanced MRI
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts 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
Contacts and Locations| United States, New York | |
| Memorial Sloan Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| Principal Investigator: | Ghassan Abou-Alfa | Memorial Sloan-Kettering Cancer Center |
More Information
No publications provided
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00639509 History of Changes |
| Other Study ID Numbers: | NCI-2009-00283, 08-015, CDR0000589633, N01CM62206 |
| Study First Received: | March 19, 2008 |
| Last Updated: | August 24, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Liver Neoplasms Carcinoma Carcinoma, Hepatocellular Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Digestive System Neoplasms Neoplasms by Site |
Digestive System Diseases Liver Diseases Adenocarcinoma Antibodies Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 22, 2013