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 (Multi-H...

Completed · Phase 2

Conditions studied: Head and Neck Neoplasms, Pheochromocytoma, Colorectal Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell

In brief

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.

Key facts

Study ID: NCT00923481
Run by: National Cancer Institute (NCI)
People needed: 37
Starts: 2009-04-01
Expected to finish: 2012-01-01
Last updated by the study team: 2015-09-30

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

3.2.1 Subjects who have had chemotherapy, biotherapy, or radiotherapy within 4 weeks prior to entering the study, or those who have not recovered from adverse events due to prior therapy.
A time period of greater than or equal to 2 weeks must have elapsed since a patient was administered any investigational agent as part of a Phase 0 study (also referred to as an early Phase I study or pre-Phase I study where a sub-therapeutic dose of drug is administered) at the principal investigator's (PI's) discretion, and patients should have recovered from any toxicity from prior therapy to eligibility levels.
3.2.2 Patients must not have other current malignancies, other than basal cell skin cancer, squamous cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast.
Patients who have undergone primary therapy for a prior diagnosis of cancer and are disease free for at least 3 years prior to study entry will be included in the trial.
3.2.3 Patients may not be receiving any other investigational agents.
3.2.4 Subjects with known brain metastases are excluded with the exception of those whose brain metastatic disease status has remained stable for at least 3 months since treatment of the brain metastases without steroids (except for maintenance replacement doses) or antiseizure medications.
Patients cannot be taking enzyme-inducing anti-seizure medications (e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbamazepine); other seizure medications that are not considered enzyme-inducing would be permissible.
3.2.5 Because there is an unknown but potential risk for adverse events in nursing infants secondary to exposure to this agent, women who are breast feeding are ineligible for this study.
3.2.6 Patients receiving medications known to induce/inhibit cytochrome P450 3A4 (CYP3A4) will be excluded from this study.
Patients who must initiate treatment with a CYP3A4 inhibitor while receiving R935788 will be carefully monitored.
Inhibitors of CYP3A4 include but are not limited to:
amiodarone,
clarithromycin,
erythromycin,
imatinib,
troleandomycin,
ritonavir,
indinavir,
fluconazole,
itraconazole,
and ketoconazole.
Patients should also avoid grapefruit and grapefruit juice during participation in the study.
Patients will also be required to keep a study diary to record any side effects that occur during the study and any other medications taken.
3.2.7 Subjects with clinically significant illnesses which would compromise participation in the study, including, but not limited to: unstable or serious medical conditions (ongoing or active infection, symptomatic congestive heart failure [AHA Class II or worse], unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements) are excluded due to the possibility that the underlying condition may obscure the attribution of effect and adverse events with respect to the study medication and may limit study compliance.
3.2.8 Patients with hepatocellular cancer (HCC) may have underlying chronic infectious hepatitis as long as there is no evidence of hepatic failure and they meet the eligibility criteria.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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