- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02058017
OPB-51602 in Locally Advanced Nasopharyngeal Carcinoma Prior to Definitive Chemoradiotherapy
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
Study Overview
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 Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Singapore, Singapore, 119228
- National University Hospital, Singapore
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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:
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.
Exclusion Criteria:
- 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.
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part I & Part II
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. |
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Recommended Phase II dose of OPB-51602
Time Frame: 1 year
|
1 year
|
Collaborators and Investigators
Investigators
- Principal Investigator: Andrea Wong, MBBS, National University Hospital, Singapore
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Pharyngeal Neoplasms
- Otorhinolaryngologic Neoplasms
- Head and Neck Neoplasms
- Nasopharyngeal Diseases
- Pharyngeal Diseases
- Stomatognathic Diseases
- Otorhinolaryngologic Diseases
- Nasopharyngeal Neoplasms
- Carcinoma
- Nasopharyngeal Carcinoma
Other Study ID Numbers
- NP01/27/13
- 2013/00691 (Other Identifier: NHG Domain Specific Review Board)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Nasopharyngeal Carcinoma
-
National Cancer Institute (NCI)NRG OncologyTerminatedRecurrent Nasopharyngeal Carcinoma | Stage IV Nasopharyngeal Carcinoma AJCC v8 | Metastatic Nasopharyngeal Carcinoma | Metastatic Nasopharyngeal Keratinizing Squamous Cell Carcinoma | Metastatic Nasopharyngeal Nonkeratinizing Carcinoma | Metastatic Nasopharyngeal Undifferentiated Carcinoma | Nasopharyngeal... and other conditionsUnited States, Canada, China, Singapore
-
National Cancer Institute (NCI)CompletedRecurrent Nasopharynx Carcinoma | Stage III Nasopharyngeal Carcinoma AJCC v7 | Stage IV Nasopharyngeal Carcinoma AJCC v7 | Stage IVA Nasopharyngeal Carcinoma AJCC v7 | Stage IVB Nasopharyngeal Carcinoma AJCC v7 | Stage IVC Nasopharyngeal Carcinoma AJCC v7 | Nasopharyngeal Nonkeratinizing CarcinomaUnited States, Singapore, China
-
National Cancer Institute (NCI)Radiation Therapy Oncology GroupCompletedStage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 | Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7 | Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 | Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 | Stage III Nasopharyngeal...United States, Canada
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedStage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 | Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7 | Stage I Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7 | Stage I Nasopharyngeal Undifferentiated Carcinoma AJCC v7 | Stage II Nasopharyngeal Keratinizing... and other conditionsUnited States, Canada, Australia
-
Alain AlgaziAstraZeneca; Incyte CorporationWithdrawnRecurrent Nasopharyngeal Carcinoma | Metastatic Nasopharyngeal Carcinoma | Stage IV Nasopharyngeal Carcinoma | Epstein-Barr Virus Positive | Stage III Nasopharyngeal Carcinoma | Stage IVA Nasopharyngeal Carcinoma | Stage IVB Nasopharyngeal Carcinoma
-
Alliance for Clinical Trials in OncologyNot yet recruitingRecurrent Nasopharyngeal Carcinoma | Stage IV Nasopharyngeal Carcinoma AJCC v8 | Metastatic Nasopharyngeal Carcinoma
-
Gustave Roussy, Cancer Campus, Grand ParisUnknownLOCALLY ADVANCED UNDIFFERENTIATED CARCINOMA NASOPHARYNGEAL TYPE UCNTFrance
-
Stanford UniversityTerminatedStage IV Nasopharyngeal Carcinoma | Stage III Nasopharyngeal Carcinoma | Stage IVA Nasopharyngeal Carcinoma | Stage IVB Nasopharyngeal Carcinoma | Stage II Nasopharyngeal Carcinoma | Stage 0 Nasopharyngeal Carcinoma | Stage 0 Paranasal Sinus Cancer | Stage I Nasopharyngeal Carcinoma | Stage I Paranasal... and other conditionsUnited States
-
National Cancer Institute (NCI)Not yet recruitingStage IV Nasopharyngeal Carcinoma AJCC v8 | Stage II Nasopharyngeal Carcinoma AJCC v8 | Stage III Nasopharyngeal Carcinoma AJCC v8
-
Cancer Institute and Hospital, Chinese Academy...RecruitingRecurrent Nasopharyngeal Carcinoma | Metastatic Nasopharyngeal CarcinomaChina
Clinical Trials on OPB-51602
-
Otsuka Pharmaceutical Co., Ltd.CompletedAcute Myeloid Leukemia | Multiple Myeloma | Non-Hodgkin Lymphoma | Chronic Myeloid Leukemia | Acute Lymphoid LeukemiaJapan
-
Otsuka Pharmaceutical Development & Commercialization...CompletedAdvanced CancerUnited States
-
Otsuka Beijing Research InstituteCompletedMalignant Solid TumourSingapore
-
Otsuka Pharmaceutical Co., Ltd.CompletedHepatocellular CarcinomaJapan
-
Hospital Universitario 12 de OctubreApices Soluciones S.L.; Otsuka Pharmaceutical Co., Ltd.; Vivia BiotechCompletedAcute Myeloid LeukemiaSpain
-
Otsuka Beijing Research InstituteOtsuka Pharmaceutical Co., Ltd.UnknownNon-Hodgkin's Lymphoma(NHL) | Multiple Myeloma(MM)Hong Kong
-
Otsuka Pharmaceutical Development & Commercialization...Completed
-
Korea Otsuka Pharmaceutical Co., Ltd.UnknownSolid TumorKorea, Republic of
-
Korea Otsuka Pharmaceutical Co., Ltd.Otsuka Pharmaceutical Co., Ltd.CompletedSolid TumorKorea, Republic of
-
National University Hospital, SingaporeOtsuka Pharmaceutical Co., Ltd.Unknown