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

NCT01711034 | Completed Phase 1

• 1 other identifier: 317-11-201
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the safe and tolerable dose level of OPB-111077 for patients with advanced cancer.

Conditions

Solid Tumors

Keywords

Solid tumors

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of OPB-111077

  AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status

  28 Days

Secondary Outcomes (6)

• To determine the pharmacokinetics of OPB-111077

  28 Days

• Pharmacodynamic profile

  28 Days

• Antitumor effects

  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

  Within the first cycle [28 days].

• PET Sub-study (Part C)

  2 weeks

Study Arms (1)

OPB-111077

EXPERIMENTAL

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

Interventions

OPB-111077 DRUG

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.

OPB-111077

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (1)

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 29511132 DERIVED

Study Officials

• Edwin Rock, MD, PhD

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2012
• First Posted: October 22, 2012
• Study Start: June 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: April 5, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)