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 safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01711034
Recruitment Status : Completed
First Posted : October 22, 2012
Last Update Posted : April 5, 2016
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: OPB-111077 Phase 1

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  (Clinical Trial)
Actual Enrollment : 145 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : June 2012
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

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.

Primary Outcome Measures :
  1. Safety and tolerability of OPB-111077 [ Time Frame: 28 Days ]
    AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status

Secondary Outcome Measures :
  1. To determine the pharmacokinetics of OPB-111077 [ Time Frame: 28 Days ]
    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).

  2. Pharmacodynamic profile [ Time Frame: 28 Days ]
    Study drug effects on STAT3 phosphorylation in response to IL-6 will be measured in PBMCs from subjects treated with OPB-111077.

  3. 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. ]
    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.

  4. To determine the MTD of OPB-111077 [ Time Frame: Within the first cycle [28 days]. ]
    The highest dose at which fewer than 2 of 6 subjects experience DLT during the first 28 day cycle.

  5. PET Sub-study (Part C) [ Time Frame: 2 weeks ]
    A sub-study of up to 24 patients with PET-avid tumors where additional PET scans are performed to explore intra-subject PET activity.

  6. Food-effect Sub-study (Part B) [ Time Frame: 11 days ]
    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.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01711034

United States, Texas
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study Director: Edwin Rock, MD, PhD Otsuka Pharmaceutical Development & Commercialization, Inc.

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc. Identifier: NCT01711034     History of Changes
Other Study ID Numbers: 317-11-201
First Posted: October 22, 2012    Key Record Dates
Last Update Posted: April 5, 2016
Last Verified: April 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Solid tumors