An Open-Label Phase I Study to Determine the Safety, Pharmacokinetics and Pharmacodynamics of JNJ-26481585 in Subjects With Advanced Stage and/or Refractory Solid Malignancies and Lymphomas
JNJ-24681585 is a histone deacetylase (HDAC) inhibitor. It is a drug in development for
treatment of cancer. In this study, the safety (the effect on the body) of the drug in
patients with advanced or refractory solid malignancies or lymphoma will be studied. The
maximum dose that can be tolerated by patients will be determined. The absorption, break
down, and elimination of the drug will be studied and in some patients the effect of food on
these processes will be examined. Antitumor activity of JNJ-26481585 will be evaluated.
JNJ-26481585 will be administered in a continuous regimen with 21-day treatment cycles. The
dose of JNJ-26481585 will start low and will be increased during the study in groups of 2 to
6 patients. The dose each patient receives at study entry will not increase, but patients
who receive drug at a later enrollment time may receive a higher dose. 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. Once a safe dose level has been determined an additional group of 12-24 patients
will be treated.
The amount of JNJ-26481585 in the blood will be measured and the effect on the disease will
be evaluated in all patients. In some patients, the effect of food on the absorption, break
down, and elimination of the study drug will also be studied.
Patients will be screened for eligibility within 4 weeks before study treatment is given.
The treatment will consist of 21-day treatment cycles in a continuous once daily dosing
regimen. 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 to include days when there is no treatment (a pause) as guided by clinical
observations. The dosing regimen may be adjusted to twice daily or three times daily intake
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
During the first treatment cycle, patients are required to stay in the hospital for 3 or 4
nights. In addition there are 8 or 9 daytime visits during Cycles 1 and 2 (combined) that
may take up to 12 hours after the morning dose at 2 or 3 occasions and up to 4 hours after
the morning dose at the other 6 occasions. From Cycle 3 onwards, there is only 1 daytime
visit 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 patients illness. Two weeks after the last dose of the study drug,
patients are required to return to the study site for follow-up assessments. JNJ-26481585
will be provided as capsules and will be taken by mouth once daily throughout treatment. The
starting dose level will be 2 mg but the dose received by an individual patient will be
determined at the time of enrollment. Modifications to the treatment schedule or dosing
regimen may be explored during the course of this study. Patients can continue receiving
treatment as long as there is benefit as evaluated by the study doctor and there are no
unacceptable side effects.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Determine the safety and the maximum tolerated dose of JNJ-26481585. Determine how JNJ-26481585 and its metabolite, JNJ-26395018, are absorbed, broken down and eliminated after oral administration
Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
United States: Institutional Review Board