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

Nasopharyngeal Carcinoma Clinical Trial

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

Status Terminated

Clinical 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. 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.

Clinical Trial 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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

• NCT number: NCT02058017
• Study type: Interventional
• Source: National University Hospital, Singapore
• Status: Terminated
• Phase: Phase 1
• Start date: November 2013
• Completion date: May 2015