Clinical trial NCT00639509: IMC-A12 in Treating Patients With Advanced Liver Cancer
Official title: A Phase 2 Study of IMC-A12 (NSC742460) in Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Localized Unresectable Adult Primary Liver Cancer
Recurrent Adult Primary Liver Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-03-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: PFS Rate
timeFrame: At 4 months
measure: Best Overall Response Rate (ORR)
timeFrame: From the start of the treatment until disease progression/recurrence
Secondary outcomes:
measure: Median Overall Survival
timeFrame: Post-Treatment
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Ghassan Abou-Alfa
role: PRINCIPAL_INVESTIGATOR
References: