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

NCT ID: NCT01711034

Last Updated: 2016-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2015-12-31

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.

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.

Conditions

Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

OPB-111077

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edwin Rock, MD, PhD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29511132 (View on PubMed)

Other Identifiers

317-11-201

Identifier Type: -

Identifier Source: org_study_id