Clinical trial NCT01711034: A Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once Daily OPB-111077 in Subjects With Advanced Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: Solid tumors
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2012-10-22
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Safety and tolerability of OPB-111077
timeFrame: 28 Days
Secondary outcomes:
measure: To determine the pharmacokinetics of OPB-111077
timeFrame: 28 Days
measure: Pharmacodynamic profile
timeFrame: 28 Days
measure: Antitumor effects
timeFrame: 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.
measure: To determine the MTD of OPB-111077
timeFrame: Within the first cycle [28 days].
measure: PET Sub-study (Part C)
timeFrame: 2 weeks
measure: Food-effect Sub-study (Part B)
timeFrame: 11 days
Other outcomes:
Locations:
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Edwin Rock, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.