Multicenter, open-label, phase 1, cohort dose escalation study to determine the maximum tolerated dose (MTD) of 3 intermittent OSI-906 dosing schedules.
Multicenter, open-label, phase 1, cohort dose escalation. The study will open with Dosing Schedule 1 (S1) (OSI-906 Once Daily (QD) Days 1-3 every 14 days). Dosing Schedule 2 (S2) (OSI-906 QD Days 1-5 every 14 days) will be initiated following observation of clinically significant related toxicity ≥ grade 2 in S1 or after a review of preliminary safety and pharmacokinetic data from ≥ 6 dose levels in S1 indicate that toxicity is acceptable and potential improvement in exposure may be achieved by an increased number of dosing days. Dosing Schedule 3 (S3) (OSI-906 QD Days 1-7 every 14 days) will occur upon observation of clinically significant related toxicity ≥ grade 2 in S2 or after ≥ 1 dose level in S2 has been examined. A 3-patient bridging dose cohort will be opened in S1 to qualitatively compare the 25 mg capsule with 100 mg capsule dosage strengths in order to confirm that no gross differences in safety or exposure exist between the formulations. In order to characterize the tablet, a 6-patient dose cohort will be opened to qualitatively examine the pharmacokinetics of this dosage form. Once the MTD has been determined for S1 and once the safety and pharmacokinetic data from the tablet cohort have been reviewed, a Fed-Fasted Expansion Cohort will be opened.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
79
Oral OSI-906 administered on an intermittent schedule at increasing doses until disease progression or unacceptable toxicity
MD Anderson Cancer Center
Houston, Texas, United States
Drug Development Unit, Royal Marsden Hospital
Sutton, Surrey, United Kingdom
Determine the maximum tolerated dose (MTD) for each of 3 intermittent schedules and establish a recommended phase 2 dose of OSI-906
Time frame: 14 days
Safety profile, Pharmacokinetic profile, Pharmacodynamic relationships Preliminary antitumor activity
Time frame: 3 years
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