A Phase I Study to Evaluate the Safety and Pharmacokinetics of R306465 in Subjects With Advanced Solid Malignancies
A Phase I Study to Evaluate the Safety and Pharmacokinetics of R306465 in Subjects With Advanced Solid Malignancies
The purpose of this study is to assess the safety of R306465 (a drug in development for cancer) in patients with advanced cancer on the maximum dose that can be tolerated. Also, the absorption, breakdown and elimination of the drug will be studied.
R306465, a histone deacetylase (HDAC) inhibitor, is a new drug in development for cancer. In this study, the safety (the effect on the body) of R306465 in patients with advanced cancer will be studied and the maximum dose that can be tolerated by these patients will be determined. The absorption, break down, and elimination of the drug will be studied. Antitumor activity of R306465 will be evaluated.
R306465 will be administered in a continuous regimen for 21 days followed by a 1-week rest period, which constitutes a 28-day treatment cycle. The dose of R306465 will start low and will be increased during the study in groups of 3 to 6 patients. If a group of patients does not have severe side effects, the next group of patients will get a higher dose. The dose will increase until some patients have severe side effects. The dose will then be decreased to a dose level where severe side effects are observed in less than 1/3 of patients. The amount of R306465 in the blood will be measured and the effect on the disease will be evaluated in all patients.
Patients will be screened for eligibility within 4 weeks before study treatment is given. The duration of treatment will depend on adverse effects and whether there is benefit from the treatment.
The design of a cycle may be adjusted during the course of the study as guided by clinical observations. The dosing regimen may be adjusted as guided by information on how rapidly your body breaks down and eliminates the study drug. Patients will be informed if there are changes in the design of a cycle or the dosing regimen.
During the first treatment cycle, patients are required to stay in the hospital for at least 3 nights. In addition there are 6 daytime visits during Cycles 1 and 2 (combined) that may take up to 4 hours after the morning dose. From Cycle 3 onwards, there are only 2 daytime visits per treatment cycle, and these visits usually take up less time.
Throughout the study, especially during Cycles 1 and 2, patients will undergo frequent blood and urine tests, procedures to assess safety including heart function, and tests to assess the course of the patient's illness. Two weeks after the last dose of the study drug, patients are required to return to the study site for follow-up assessments. R306465 will be administered orally once daily for 21 consecutive days followed by a 1-week rest period. These 4 weeks will constitute 1 treatment cycle. The starting dose level will be 100mg. The dose for each patient will be assigned at enrollment. On the basis of assessment by the investigator, the patient may continue to receive study drug as long as there is clinical benefit and in absence of intolerable side effects.
Inclusion Criteria:
Exclusion Criteria: