OPB-51602 in Locally Advanced Nasopharyngeal Carcinoma Prior to Definitive Chemoradiotherapy

NCT02058017 | Terminated Phase 1 DMC

• 2 other identifiers: NP01/27/132013/00691
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II dose of OPB-51602

  1 year

Study Arms (1)

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.

Drug: OPB-51602

Interventions

OPB-51602 DRUG

Also known as: OPB-51602 OPB-51602 is an inhibitor of STAT3 phosphorylation developed by Otsuka Pharmaceuticals, Japan.

Part I & Part II

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator
• Shin Nippon Biomedical Laboratories, Ltd.: collaborator

Study Sites (1)

National University Hospital, Singapore

Singapore, 119228, Singapore

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Study Officials

• Andrea Wong, MBBS

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: February 7, 2014
• Study Start: November 1, 2013
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: June 19, 2015

Record last verified: 2015-06

Locations

SG (1)