Nasopharyngeal CarcinomaPhase 1NCT02058017
OPB-51602 in Locally Advanced Nasopharyngeal Carcinoma Prior to Definitive Chemoradiotherapy
A Phase 1 study testing OPB-51602 in people with Nasopharyngeal Carcinoma, run by National University Hospital, Singapore at 1 site in Singapore.
Trial summary
This is a lead-in dose escalation study to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), and recommended Phase II dose of OPB-51602 administered on a weekly basis in subjects with advanced malignancies. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Nasopharyngeal Carcinoma
- What is being tested?
- OPB-51602
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteSingapore
- Study dates
- Nov 2013to May 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Part I only: Patients with pathologically confirmed, locally recurrent or metastatic solid tumours who have failed standard treatment options. In the enrichment cohort, NPC patients will be eligible as long as they have received prior platinum-based therapy, either in the curative or metastatic setting. At least one tumour lesion (primary or metastatic) that is suitable for baseline biopsy which is accessible either by free hand or image guided biopsy is required.
- Part II only: Patients with histologically confirmed WHO Type III NPC. Tumour stage III, IVA (T4 N0-2 M0) or IVB (Any T N3 M0) according to the American Joint Committee on Cancer (AJCC) 2010 criteria and planned for definitive chemoradiotherapy (radiotherapy at 70Gy/33# with concurrent IV cisplatin 40mg/m2/week for duration of radiotherapy) as per institutional standards. Patients who are planned for induction chemotherapy followed by concurrent chemoradiotherapy will not be included in the study. Patients receiving alternative chemoradiotherapy regimens may only be considered upon approval of the P.I.
- Age ≥ 21 years at the time of consent
- Eastern Cooperative Oncology Group (ECOG) performance status < 1
- Life expectancy > 3 months
- Adequate organ function as defined by:
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- Bone marrow function
- Haemoglobin ≥ 9g/dl
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 75 x 109/L. Liver function
- Bilirubin </= 2.5x upper limit of normal (ULN)
- Alanine transaminase (ALT) and aspartate transaminase (AST) </= 2.5x ULN or </= 5x ULN if liver metastases are present
- Prothrombin time (PT) within the normal range for the institution. Renal function
- Plasma creatinine </=1.5x institutional ULN for part I and calculated creatinine clearance (by the Cockcroft-Gault formula) > 60mL/min for part II.
- Capable of swallowing OPB-51602 tablets
- Recovery from any previous drug- or procedure-related toxicity to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 Grade 0 or 1 (except alopecia), or to baseline preceding the prior treatment.
- Signed informed consent obtained before any study specific procedure. Subjects must be able to understand and be willing to sign the written informed consent.
Who cannot join
- Part I only: Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 4 weeks of starting investigational medicinal product (IMP).
- Part II only: Previous or concurrent anti-cancer chemotherapy, immunotherapy, radiotherapy or any other investigational therapy.
- Uncontrolled central nervous system metastasis (applicable to Part I)
- Any concomitant condition that could compromise the objectives of this study and/or the patient's compliance (eg. severe medical conditions such as uncontrolled infection, poorly controlled diabetes mellitus, hypercalcaemia, psychiatric disorders).
- Use of any of the prohibited medications and other substances listed in Appendix 2 (CYP3A4 Inhibitors and Inducers) within 1 week prior to start of study drug administration
- Pregnancy or breastfeeding.
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- Women of childbearing potential not employing adequate contraception. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of study medication, and a negative result must be documented before start of study medication. Women of childbearing potential and men, must agree to use adequate contraception (barrier method of birth control) upon signing the informed consent form until at least 3 months after the last study drug administration.
- Known or suspected allergy to the investigational agent or any agent given in association with this study.
- Previous or concurrent cancer which is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumours (Ta, Tis \& T1) or any cancer curatively treated > 3 years prior to study entry.
- Interstitial lung disease with ongoing signs and symptoms at the time of screening.
- Patients with CTCAE Grade 2 or higher peripheral neuropathy.
- Patients with CTCAE Grade 1 or higher pneumonitis (interstitial pneumonia) or pulmonary fibrosis
- History of significant cardiac disease: congestive cardiac failure > NYHA class II, ongoing unstable angina, new-onset angina or myocardial infarction within the past 3 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Signal Transducer and Activator of Transcription (STAT)3 Pathway and the Development of STAT3 Phosphorylation Inhibitors as Cancer Therapy: Lead-In Phase I Dose-Escalating, Open-Label, Non-Randomised Study of A Weekly Regimen OPB-51602 in Advanced Refractory Solid Tumours With Enrichment Cohorts of Nasopharyngeal Carcinoma Followed By A Biomarker Study Evaluating OPB-51602 in Locally Advanced Nasopharyngeal Carcinoma Prior to Definitive Chemoradiotherapy
This is a lead-in dose escalation study to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), and recommended Phase II dose of OPB-51602 administered on a weekly basis in subjects with advanced malignancies. Using the recommended phase II dose, the efficacy and tolerability of OPB-51602 administered prior to definitive chemoradiotherapy will be evaluated in locally advanced NPC patients. This study's overarching goal is the development of STAT3 inhibitors as a novel class of anti-cancer agents and the optimization of patient selection for STAT3 inhibitor therapy through parallel biomarker studies. This study hopes to establish a therapeutic window for OPB-51602 in solid tumours and will evaluate its potential as a targeted therapy of NPC, since this represents a critical unmet clinical need. The development of predictive and pharmacodynamic biomarkers in tandem with the clinical evaluation of OPB-51602 will be crucial to its therapeutic advancement and will enable an understanding of the genetic contexts of responsiveness and resistance to OPB-51602, which can in turn lead to the development of effective drug combinations to overcome resistance.The study hypothesizes that OPB-51602, a first-in-class STAT3 inhibitor, is efficacious in solid tumours with constitutively activated STAT3, such as NPC.
Read the detailed description
Part I This is a lead-in dose-finding, open-label, non-randomised study of OPB-51602 in patients with advanced refractory solid tumours who have biopsy-amenable lesions at study entry. Using a starting dose of 10mg per week, an accelerated dose titration escalation followed by a 3+3 design will be employed until MTD and recommended weekly dose are determined. Following this, an expansion cohort of 10 patients will be enrolled to establish safety of the recommended phase II dose. Additionally, it is also planned to explore the efficacy of the agent in an enrichment cohort of approximately 10 metastatic NPC patients. One treatment cycle is defined as a period of 28 days. Tumour biopsies will be performed at baseline while blood sampling for circulating biomarkers will be performed on days 1, 2, 3, 8, 22 and upon completion of OPB-51602 dosing. Pharmacokinetic sampling will be done on Cycle 1 Days 1, 8 and 22. Safety assessments will be performed weekly till week 8, bi-weekly till week 16, then monthly thereafter and response assessments will be performed every 8 weeks. The number of subjects estimated to participate in this study will depend on the number of cohorts enrolled.
Part II This is a single-centre, open-label non-randomised phase II study evaluating OPB-51602 in stage III-IVB NPC conducted in the window period prior to definitive chemoradiotherapy. Eligible patients will receive OPB-51602 on a weekly basis (Day 1, 8, 15) at the recommended dose determined in part I for a total of 15 days prior to definitive chemoradiotherapy. Response assessment will be performed after OPB-51602 dosing on day 15 using PET/CT scans and clinical tumour measurements, while other radiologic assessments will be performed on the completion of chemoradiotherapy. Safety assessments will be performed at weekly intervals until day 22 or until toxicities related to the study treatment have been resolved. Tumour biopsies will be performed at baseline and day 15 while circulating biomarker studies will be performed on days 1, 2, 3, 8, 15 and upon completion of chemoradiotherapy. There is no mandated rest period between the administration of study drug and definitive chemoradiotherapy. The decision to proceed with chemoradiotherapy is at the discretion of individual investigators, provided the subject has recovered or is recovering from all significant toxicities of the study drug. Chemoradiotherapy should be in accordance with the institutional standard and induction chemotherapy is not permitted. Proposed alternative treatment regimens must receive the approval of the Principal Investigator.
- Conditions
- Nasopharyngeal Carcinoma
- Being tested
- OPB-51602
- Medical subject headings
- Nasopharyngeal Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OPB-51602Drug
Also called OPB-51602 OPB-51602 is an inhibitor of STAT3 phosphorylation developed by Otsuka Pharmaceuticals, Japan.
| Study group | Role | What they receive |
|---|---|---|
| Part I & Part II | Experimental | Part I - This is a lead-in dose-finding, open-label, non-randomised arm of the study: Using a starting dose of 10mg per week, an accelerated dose titration escalation followed by a 3+3 design will be employed until MTD and recommended weekly dose are determined.
Part II - This is a single-centre, open-label non-randomised phase II study evaluating OPB-51602 in stage III-IVB NPC conducted in the window period prior to definitive chemoradiotherapy. Eligible patients will receive OPB-51602 on a weekly basis (Day 1, 8, 15) at the recommended dose determined in part I for a total of 15 days prior to definitive chemoradiotherapy. Receives: Drug: OPB-51602 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended Phase II dose of OPB-51602
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2014 (estimated)
- Study startNov 2013
- Primary completionMay 2015
- Study completionMay 2015
Why it stopped: Lactic and metabolic acidosis of OPB-51602 is not tolerable
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe 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
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Otsuka Pharmaceutical Co., Ltd., Shin Nippon Biomedical Laboratories, Ltd.
- Responsible party
- Sponsor
- Investigators
- Andrea Wong, MBBS, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02058017
- Sponsor's protocol ID
- NP01/27/13
- Other IDs
- 2013/00691
- Status last verified
- Jun 2015
- First submitted
- 15 Jan 2014
- Last updated
- 19 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Signal Transducer and Activator of Transcription (STAT)3 Pathway and the Development of STAT3 Phosphorylation Inhibitors as Cancer Therapy: Lead-In Phase I Dose-Escalating, Open-Label, Non-Randomised Study of A Weekly Regimen OPB-51602 in Advanced Refractory Solid Tumours With Enrichment Cohorts of Nasopharyngeal Carcinoma Followed By A Biomarker Study Evaluating OPB-51602 in Locally Advanced Nasopharyngeal Carcinoma Prior to Definitive Chemoradiotherapy
- ClinicalTrials.gov ID
- NCT02058017
- Acronym / sponsor ID
- NP01/27/13
- Conditions
- Nasopharyngeal Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lactic and metabolic acidosis of OPB-51602 is not tolerable
- Enrolment
- 9 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Collaborators
- Otsuka Pharmaceutical Co., Ltd., Shin Nippon Biomedical Laboratories, Ltd.
- Study start
- Nov 2013
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 7 Feb 2014 (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.
This is a lead-in dose escalation study to determine the safety, tolerability, pharmacokinetics, maximum tolerated dose (MTD), and recommended Phase II dose of OPB-51602 administered on a weekly basis in subjects with advanced malignancies. Using the recommended phase II dose, the efficacy and tolerability of OPB-51602 administered prior to definitive chemoradiotherapy will be evaluated in locally advanced NPC patients. This study's overarching goal is the development of STAT3 inhibitors as a novel class of anti-cancer agents and the optimization of patient selection for STAT3 inhibitor therapy through parallel biomarker studies. This study hopes to establish a therapeutic window for OPB-51602 in solid tumours and will evaluate its potential as a targeted therapy of NPC, since this represents a critical unmet clinical need. The development of predictive and pharmacodynamic biomarkers in tandem with the clinical evaluation of OPB-51602 will be crucial to its therapeutic advancement and will enable an understanding of the genetic contexts of responsiveness and resistance to OPB-51602, which can in turn lead to the development of effective drug combinations to overcome resistance.The study hypothesizes that OPB-51602, a first-in-class STAT3 inhibitor, is efficacious in solid tumours with constitutively activated STAT3, such as NPC.
Detailed description
Part I This is a lead-in dose-finding, open-label, non-randomised study of OPB-51602 in patients with advanced refractory solid tumours who have biopsy-amenable lesions at study entry. Using a starting dose of 10mg per week, an accelerated dose titration escalation followed by a 3+3 design will be employed until MTD and recommended weekly dose are determined. Following this, an expansion cohort of 10 patients will be enrolled to establish safety of the recommended phase II dose. Additionally, it is also planned to explore the efficacy of the agent in an enrichment cohort of approximately 10 metastatic NPC patients. One treatment cycle is defined as a period of 28 days. Tumour biopsies will be performed at baseline while blood sampling for circulating biomarkers will be performed on days 1, 2, 3, 8, 22 and upon completion of OPB-51602 dosing. Pharmacokinetic sampling will be done on Cycle 1 Days 1, 8 and 22. Safety assessments will be performed weekly till week 8, bi-weekly till week 16, then monthly thereafter and response assessments will be performed every 8 weeks. The number of subjects estimated to participate in this study will depend on the number of cohorts enrolled.
Part II This is a single-centre, open-label non-randomised phase II study evaluating OPB-51602 in stage III-IVB NPC conducted in the window period prior to definitive chemoradiotherapy. Eligible patients will receive OPB-51602 on a weekly basis (Day 1, 8, 15) at the recommended dose determined in part I for a total of 15 days prior to definitive chemoradiotherapy. Response assessment will be performed after OPB-51602 dosing on day 15 using PET/CT scans and clinical tumour measurements, while other radiologic assessments will be performed on the completion of chemoradiotherapy. Safety assessments will be performed at weekly intervals until day 22 or until toxicities related to the study treatment have been resolved. Tumour biopsies will be performed at baseline and day 15 while circulating biomarker studies will be performed on days 1, 2, 3, 8, 15 and upon completion of chemoradiotherapy. There is no mandated rest period between the administration of study drug and definitive chemoradiotherapy. The decision to proceed with chemoradiotherapy is at the discretion of individual investigators, provided the subject has recovered or is recovering from all significant toxicities of the study drug. Chemoradiotherapy should be in accordance with the institutional standard and induction chemotherapy is not permitted. Proposed alternative treatment regimens must receive the approval of the Principal Investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Part I & Part II | Experimental | Drug: OPB-51602Part I - This is a lead-in dose-finding, open-label, non-randomised arm of the study: Using a starting dose of 10mg per week, an accelerated dose titration escalation followed by a 3+3 design will be employed until MTD and recommended weekly dose are determined. Part II - This is a single-centre, open-label non-randomised phase II study evaluating OPB-51602 in stage III-IVB NPC conducted in the window period prior to definitive chemoradiotherapy. Eligible patients will receive OPB-51602 on a weekly basis (Day 1, 8, 15) at the recommended dose determined in part I for a total of 15 days prior to definitive chemoradiotherapy. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Part I only: Patients with pathologically confirmed, locally recurrent or metastatic solid tumours who have failed standard treatment options. In the enrichment cohort, NPC patients will be eligible as long as they have received prior platinum-based therapy, either in the curative or metastatic setting. At least one tumour lesion (primary or metastatic) that is suitable for baseline biopsy which is accessible either by free hand or image guided biopsy is required.
- Part II only: Patients with histologically confirmed WHO Type III NPC. Tumour stage III, IVA (T4 N0-2 M0) or IVB (Any T N3 M0) according to the American Joint Committee on Cancer (AJCC) 2010 criteria and planned for definitive chemoradiotherapy (radiotherapy at 70Gy/33# with concurrent IV cisplatin 40mg/m2/week for duration of radiotherapy) as per institutional standards. Patients who are planned for induction chemotherapy followed by concurrent chemoradiotherapy will not be included in the study. Patients receiving alternative chemoradiotherapy regimens may only be considered upon approval of the P.I.
- Age ≥ 21 years at the time of consent
- Eastern Cooperative Oncology Group (ECOG) performance status < 1
- Life expectancy > 3 months
Key exclusion criteria (13 listed)
- Part I only: Chemotherapy, radiotherapy, surgery, immunotherapy or other therapy within 4 weeks of starting investigational medicinal product (IMP).
- Part II only: Previous or concurrent anti-cancer chemotherapy, immunotherapy, radiotherapy or any other investigational therapy.
- Uncontrolled central nervous system metastasis (applicable to Part I)
- Any concomitant condition that could compromise the objectives of this study and/or the patient's compliance (eg. severe medical conditions such as uncontrolled infection, poorly controlled diabetes mellitus, hypercalcaemia, psychiatric disorders).
- Use of any of the prohibited medications and other substances listed in Appendix 2 (CYP3A4 Inhibitors and Inducers) within 1 week prior to start of study drug administration
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-51602Also: OPB-51602 OPB-51602 is an inhibitor of STAT3 phosphorylation developed by Otsuka Pharmaceuticals, Japan. | Drug | Part I & Part II |
Primary outcome
Recommended Phase II dose of OPB-51602
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Lactic and metabolic acidosis of OPB-51602 is not tolerable). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2015.
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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.
Andrea Wong, MBBS principal investigator
National University Hospital, Singapore
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-51602 in people with Nasopharyngeal Carcinoma, run by National University Hospital, Singapore at 1 site in Singapore.
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 17 inclusion and 13 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: stopped early, as of the sponsor's last update on 19 Jun 2015. 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 Singapore. 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 was stopped early (reason given: Lactic and metabolic acidosis of OPB-51602 is not tolerable). Results are not available in the source record.
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?
Recommended Phase II dose of OPB-51602 (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Jun 2015.