A Broad Multi-Histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) in Advanced Colorectal, Non-Small Cell Lung, Head and Neck, Hepatocellular and Renal Cell Carcinomas and Pheochromocytoma and Thyroid Tumors
- R935788 (fostamatanib disodium) is a kinase inhibitor with activity in vitro against
several kinases known to be mutated or aberrantly expressed in malignant cells.
- Anticancer drugs that target multiple kinases are of particular interest because tumors
may rely on several different kinase pathways for survival.
- R935788 has shown promising activity in the NCI 60-cell line panel against colon
cancer, non-small cell lung cancer, and renal cell carcinoma cell lines, as well as in
two renal cell xenograft models. R935788 is orally absorbed in tumor-bearing mice at
concentrations that achieve antitumor activity and are not associated with observable
- Phase I studies in patients with immune thrombocytopenic purpura, rheumatoid arthritis
and lymphoma have demonstrated safety with a continuous dosing schedule, and a maximum
tolerated dose (MTD) has been established.
- To determine the clinical response of R935788 administered orally twice a day on a
continuous schedule in patients with colorectal carcinoma, pheochromocytoma,
follicular, medullary, or papillary thyroid cancer, non-small cell lung cancer,
hepatocellular carcinoma, carcinoma of the head and neck, and renal cell carcinoma.
- To evaluate the safety of R935788 in patients with various solid tumors.
- To determine the effects of R935788 on circulating tumor cells, circulating endothelial
cells and levels of phosphorylated AKT and extracellular-signal regulated kinase (ERK)
in tumor samples.
- To evaluate the biochemical response to R935788 therapy in patients with thyroid
malignancies and pheochromocytoma.
- Patients with histologically documented pheochromocytoma, follicular, medullary, or
papillary thyroid cancer, colorectal cancer, non-small cell lung carcinoma (excluding
squamous cell histology), hepatocellular carcinoma, carcinoma of the head and neck, as
well as renal cell carcinoma) whose disease has progressed after any therapy or who
have no acceptable standard treatment options.
- Radiation or chemotherapy is not permitted within 4 weeks prior to study enrollment.
- Patients must have recovered from toxicities of prior therapies to at least eligibility
-This is an open-label, Phase II study of R935788. Patients will receive R935788 orally
twice a day in 28-day cycles without interruption. Imaging studies will be obtained every 2
cycles. Following a limited dose escalation portion in each stratum, a two stage design will
be used, the initial stage of which will consist of 15 to 21 patients depending on tumor
type in each of 7 strata.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response is assessed by the RECIST (response criteria in solid tumors)criteria. A complete response (CR) is 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, progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, and stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Shivaani Kummar, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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