A First in Man Trial for Patients With Cancer
The primary objective of this study is to determine the safe and tolerable dose level of OPB-111077 for patients with advanced cancer.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once Daily OPB-111077 in Subjects With Advanced Cancer|
- Safety and tolerability of OPB-111077 [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status
- To determine the pharmacokinetics of OPB-111077 [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]The following PK parameters for Food-effect Sub-study (Cmax, AUCtau,AUCt, tmax, CLss/F and t1/2,z) will be determined using a non-compartmental approach for OPB-111077 and selected metabolites after single (Cycle 1, Day 1) and multiple daily doses (Cycle 2, Day 1).
- Pharmacodynamic profile [ Time Frame: 28 Days ] [ Designated as safety issue: Yes ]Study drug effects on STAT3 phosphorylation in response to IL-6 will be measured in PBMCs from subjects treated with OPB-111077.
- Antitumor effects [ Time Frame: Assessments will be conducted at Screening, Cycle 3, every 2 cycles (+/- 1 week) thereafter, at the Final/Early Termination Visit, and at the 30-day Follow-up Visit. ] [ Designated as safety issue: Yes ]Subjects with measurable disease will be assessed by RECIST Assessments will be conducted at Screening, Cycle 3, every 2 cycles (+/- 1 week) thereafter, at the Final/Early Termination Visit, and at the 30-day Follow-up Visit.
- To determine the MTD of OPB-111077 [ Time Frame: Within the first cycle [28 days]. ] [ Designated as safety issue: Yes ]The highest dose at which fewer than 2 of 6 subjects experience DLT during the first 28 day cycle.
- PET Sub-study (Part C) [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]A sub-study of up to 24 patients with PET-avid tumors where additional PET scans are performed to explore intra-subject PET activity.
- Food-effect Sub-study (Part B) [ Time Frame: 11 days ] [ Designated as safety issue: Yes ]An open-label, two-period crossover arm, for pre-selected study sites to determine the effect of food on the rate and extent of absorption (PK) following single dose 250mg OPB-111077.
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||April 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
In escalation stage of study, treatment with a once daily dose of OPB-111077 during cycles 1 and 2 on day 1, followed by 2-day treatment free interval, and then resuming daily dosing on day 4 through day 28. For cycle 3 and beyond, OPB-111077 will be administered for 28 continuous days per cycle until MTD is reached.
In expansion portion of study, established dose of 250mg administered once daily for 28 consecutive days for each cycle. Patient in expansion are defined as those who meet eligibility criteria and have a diagnosed malignancy that is presumed to be susceptible to inhibition by OPB-111077
Dose escalation phase starting with dose of 100mg tablets on Day 1 and 4, and all remaining days of each 28 day cycle until disease progression or toxicity develops.
Dose expansion phase starting with daily dosing of 250mg for 28 day consecutive day cycles.
The secondary objective of this study is to investigate the pharmacokinetic properties of OPB-111077; the pharmacodynamic effects of OPB-111077; the antitumor activity of OPB-111077 as assessed by RECIST or IMWG Uniform Response Criteria; and to explore whether PET responses correlate with other measures of clinical response.
|Contact: Robert J Gazak||240-683-3584||Robert.TC-Gazak@otsuka-us.com|
|United States, Texas|
|San Antonio, Texas, United States, 78229|
|Study Director:||Edwin Rock, MD, PhD||Otsuka Pharmaceutical Development & Commercialization, Inc.|