Multicenter Phase II Study of IMC-A12 in Patients With Thymoma and Thymic Carcinoma Who Have Been Previously Treated With Chemotherapy
Cisplatin-containing chemotherapy is the standard of care for advanced unresectable thymoma
and thymic carcinoma. New options for treatment are necessary in patients with advanced
thymoma and thymic carcinoma that have progressed on cisplatin-containing therapy. The
insulin-like growth factor (IGF) pathway is being studies in various malignancies including
thymoma and thymic carcinoma. IMCA12 is an anti-IGF-1R monoclonal antibody that has shown
activity in patients with thymic malignancies.
- To determine the objective response rate (partial response (PR)+complete response (CR))
to IMC-A12 monotherapy in patients with advanced or recurrent thymoma or thymic
- To evaluate time to response, duration of response, progression-free survival (PFS) and
overall survival (OS)
- To assess safety of IMC-A12
- To perform immunohistochemistry for IGF1R expression on tumor samples of thymoma and
thymic carcinoma (exploratory)
- To correlate response to therapy with changes in fludeoxyglucose 18F-positron emission
tomography (FDG-PET) imaging at baseline and first restaging
- To perform pharmacokinetic (PK) analysis of IMC-A12
- To perform pharmacodynamic (PD) analysis in blood for the detection of IGF1R, AKT and
pAKT in peripheral blood mononuclear cells (PBMC's) (exploratory).
- To assess circulating endothelial cell, circulating endothelial progenitor cells,
immune subset analysis and glucose transport in peripheral blood monocytes and
- To evaluate anti-cytokine antibodies in peripheral blood (exploratory).
- Patients with histologically confirmed thymic carcinoma or thymoma who have previously
been treated on at least one platinum-containing chemotherapy regimen
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
- Adequate renal, hepatic and hematopoietic function
- No major surgery, radiotherapy, chemotherapy or biologic therapy within 28 days of
- Patients will receive IMC-A12 at a dose of 20 mg/kg intravenously once every three
- Treatment with IMC-A12 alone will continue until disease progression
- Toxicity will be assessed every cycle by Common Terminology Criteria for Adverse Events
(CTCAE) Version 3.0 until December 31, 2010, and by CTCAE Version 4.0 beginning January
- Tumor response assessments by RECIST 1.0 criteria will be performed every 2 cycles
- Correlative studies including tissue immunohistochemistry studies will be done on
existing tumor blocks
- Blood samples will be collected for for PK's, PD's, circulating endothelial cells
(CEC's), circulating endothelial precursor cells (CEPC's), immune subsets, glucose
transport and cytokine antibodies.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective Response Rate (Partial Response (PR)+Complete Response (CR)) to IMC-A12 Monotherapy in Patients With Advanced or Recurrent Thymoma or Thymic Carcinoma.
Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is the disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Patients were assessed for response every 2 cycles (every 6 weeks) while receiving the study drug.
Giuseppe Giaccone, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|Indiana University Simon Cancer Center||Indianapolis, Indiana 46202|