A Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once Daily OPB-111077 in Subjects With Advanced 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 Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: OPB-111077

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 145
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pathologically and/or cytologically confirmed advanced malignancy that is refractory to standard therapy or for which there are no standard treatment options available
• For oral or intravenous anticancer therapies, at least 4 weeks or 5 half-lives, whichever is shorter, need to have elapsed since the last dose

• Recovery from adverse effects of prior therapy at time of enrollment to

  o ≤ Grade 1 (excluding alopecia)

• Agreement to forego any other chemotherapy, immunotherapy, radiotherapy, or investigational drug while enrolled on this trial except hormonal therapy for prostate cancer or radiotherapy for symptomatic bone metastases known to be present at Screening
• Male or female subjects aged ≥ 18 years
• ECOG performance status ≤ 2
• Adequate organ function
• Life expectancy of ≥ 3 months following trial entry
• For women of childbearing potential, a negative serum pregnancy test result at Screening
• For women of childbearing potential or men whose sexual partners are women of childbearing potential, agreement to use 2 methods of adequate contraception prior to trial entry, for the duration of the trial, and for 90 days after the last dose of trial medication
• Signed and dated IRB-approved informed consent prior to any performance of protocol-specific screening procedures

Exclusion Criteria:

• Uncontrolled concurrent illness, including but not limited to: ongoing or active infection; uncontrolled heart, liver, kidney, or endocrine disorder
• Altered mental status, psychiatric illness, or social situation that would limit compliance with trial requirements and/or obscure trial results
• Immunocompromised state
• Known or evidence of chronic viral hepatitis (hepatitis B or C virus)
• Untreated or symptomatic brain metastasis, or subjects with leptomeningeal disease
• Inability to swallow oral meds or gastrointestinal disorder that might interfere with absorption of oral drugs
• Major surgery within 28 days of first receipt of trial drug
• Nursing or pregnant women
• ≥ Grade 1 neuropathy with pain or > Grade 2 neuropathy without pain (subjects with neuropathy caused by a previous regimen that is recovered to ≤ Grade 2 and stable without pain may be included)
• Food-effect sub-study (Part B) only: Pathologies or medical histories that might impair absorption and elimination.
• PET scan sub-study (Part C) only: Uncontrollable blood glucose or intolerance to PET scan procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: OPB-111077; 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

Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of OPB-111077	AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status	28 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the pharmacokinetics of OPB-111077	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).	28 Days
Pharmacodynamic profile	Study drug effects on STAT3 phosphorylation in response to IL-6 will be measured in PBMCs from subjects treated with OPB-111077.	28 Days
Antitumor effects	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.	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	The highest dose at which fewer than 2 of 6 subjects experience DLT during the first 28 day cycle.	Within the first cycle [28 days].
PET Sub-study (Part C)	A sub-study of up to 24 patients with PET-avid tumors where additional PET scans are performed to explore intra-subject PET activity.	2 weeks
Food-effect Sub-study (Part B)	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.	11 days

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Investigators: Study Director: Edwin Rock, MD, PhD, Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Tolcher A, Flaherty K, Shapiro GI, Berlin J, Witzig T, Habermann T, Bullock A, Rock E, Elekes A, Lin C, Kostic D, Ohi N, Rasco D, Papadopoulos KP, Patnaik A, Smith L, Cote GM. A First-in-Human Phase I Study of OPB-111077, a Small-Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers. Oncologist. 2018 Jun;23(6):658-e72. doi: 10.1634/theoncologist.2017-0325. Epub 2018 Mar 6.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: October 12, 2012
• First Submitted That Met QC Criteria: October 17, 2012
• First Posted (Estimate): October 22, 2012

Study Record Updates

• Last Update Posted (Estimate): April 5, 2016
• Last Update Submitted That Met QC Criteria: April 1, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Solid tumors
• Other Study ID Numbers: 317-11-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO