Clinical trial NCT00923481
Conditions: Head and Neck Neoplasms Pheochromocytoma Colorectal Neoplasms Carcinoma, Non-Small-Cell Lung Carcinoma, Renal Cell
Keywords: Multi-Kinase Inhibitor Neoplasms Advanced Cancer Kidney Cancer Liver Cancer Pheochromocytoma Non-Small Cell Lung Cancer Colorectal Cancer Head and Neck Cancer
Sponsor: National Cancer Institute (NCI)
Start date: 2009-04-01; Completion date: 2012-01-01
Enrollment: 37 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Background:

* The drug R935788 (fostamatanib disodium) is a kinase inhibitor (i.e., it interferes with cell communication and growth and may prevent tumor growth).
* R935788 has shown promising activity in NCI-60 (a panel of 60 diverse human cancer cell lines) against colon cancer, non-small cell lung cancer, and renal cell carcinoma cell lines, as well as in two renal cell xenograft models.
* This is an open-label, Phase II study of R935788. 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 has been established.

Objectives:

* To test an experimental drug called R935788 (fostamatinib disodium) for its ability to stop cancer growth signals, thus slowing the growth of cancer cells in laboratory testing.
* To determine the clinical response of R935788 administered orally twice a day on a continuous schedule in patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer, hepatocellular, carcinoma of the head and neck, and renal cell carcinoma.
* To evaluate the effects, safety, and biochemical response of R935788 therapy.

Eligibility:

* Patients with colorectal carcinoma, pheochromocytoma, follicular or papillary thyroid cancer, non-small cell lung cancer (excluding squamous cell histology), hepatocellular cancer, carcinoma of the head and neck, and renal cell carcinoma whose disease has progressed after any therapy or who have no acceptable standard treatment options.
* Patients must have recovered from toxicities of prior therapies to at least eligibility levels.
* Patients who have received radiation or chemotherapy within 4 weeks of study enrollment are not eligible.
* Women who are pregnant or breastfeeding are not eligible.

Design:

* Researchers will conduct the following tests and procedures during the study:

  * Clinic visits with a physical exam, including vital signs and blood pressure, every other week during cycle 1, and once a month starting with cycle 2.
  * Blood will be drawn weekly during cycle 1, every other week during cycle 2, and once a month starting with cycle 3; urine tests will be conducted depending on results of blood tests.
  * Imaging tests, such as computed tomography (CT) scans (a series of x-rays) or ultrasound (an examination using sound waves), will be done every 8 weeks while the patient is receiving R935788.
* R935788 will be administered orally twice a day for 28 days (one cycle). Imaging studies will be obtained every two cycles. Patients will fill in a diary to show when they took the medication and to note any side effects. The 28-day treatment cycle will be repeated as long as the patient is tolerating R935788 and the cancer is either stable or getting better.
* Researchers will conduct the following additional tests to see how the study is affecting the patient:

  * Other research blood samples will be collected before treatment, at cycle 1 week 3, at the beginning of cycle 2, and at 8 weeks.
  * Optional tumor biopsies will be requested before starting treatment, at cycle 1 day 28.
  * Patients with specific lesions or tumors may be asked for an optional tumor biopsy on day 8.

Detailed description:
BACKGROUND

* 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 toxicity.
* 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.

OBJECTIVES

* 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.

ELIGIBILITY

* 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 levels.

STUDY DESIGN

-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.

Arms: arm 1: 200 mg BID was the administered dose for the initial part of the study and then a phase I dose escalation was added with 100 mg as the starting dose.
Interventions: intervention 1: Fostamatinib disodium
Intervention descriptions: intervention 1: 200 mg BID was the administered dose for the initial part of the study and then a phase I dose escalation was added with 100 mg as the starting dose.

Protocol documents: