Solid TumorsPhase 1NCT01711034
A Phase 1, Open-label, Multiple Dose Escalation Trial to Determine Safety and Tolerability of Once Daily OPB-111077 in Subjects With Advanced Cancer
A Phase 1 study testing OPB-111077 in people with Solid Tumors, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
Trial summary
The primary objective of this study is to determine the safe and tolerable dose level of OPB-111077 for patients with advanced cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- OPB-111077
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
The primary objective of this study is to determine the safe and tolerable dose level of OPB-111077 for patients with advanced cancer.
Read the 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
- Being tested
- OPB-111077
- Keywords
- Solid tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPB-111077Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: OPB-111077 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of OPB-111077
AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status
Measured: 28 Days
Secondary outcomes (6)
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 11 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2012 (estimated)
- Study startJun 2012
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Edwin Rock, MD, PhD, Study director, Otsuka Pharmaceutical Development & Commercialization, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01711034
- Sponsor's protocol ID
- 317-11-201
- Status last verified
- Apr 2016
- First submitted
- 12 Oct 2012
- Last updated
- 5 Apr 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
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.
PubMed 29511132
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01711034
- Acronym / sponsor ID
- 317-11-201
- Conditions
- Solid Tumors
- Keywords
- Solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 22 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OPB-111077 | Experimental | Drug: OPB-111077In 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OPB-111077Dose 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. | Drug | OPB-111077 |
Primary outcome
Safety and tolerability of OPB-111077
Time frame: 28 Days
AEs, Vital signs,Body weight, ECGs, Laboratory tests, Performance status
6 secondary outcomes
To determine the pharmacokinetics of OPB-111077
Time frame: 28 Days
Pharmacodynamic profile
Time frame: 28 Days
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.
To determine the MTD of OPB-111077
Time frame: Within the first cycle [28 days].
PET Sub-study (Part C)
Time frame: 2 weeks
Food-effect Sub-study (Part B)
Time frame: 11 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2016.
- Derived from this study: PubMed 29511132Tolcher 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.
- Individual participant dataSharing planned: No
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Solid Tumors
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edwin Rock, MD, PhD study director
Otsuka Pharmaceutical Development & Commercialization, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OPB-111077 in people with Solid Tumors, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of OPB-111077 (time frame: 28 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01711034, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2016.