Neuroendocrine tumours (NET) associated with the gastrointestinal tract are frequently indolent but problematic as a result of potential endocrine secretory properties and metastasis often to the liver. Metastases (mNET) located in the midgut and liver often secrete vasoactive products, giving rise to the “carcinoid Syndrome,”; flushing, diarrhoea, wheezing, abdominal cramps and peripheral oedema. Treatment options for mNET include surgical resection, chemoablation, and use somatostatin analogues (e.g. octreotide, lantreotide) or radio-labelled analogues (e.g. Lutate/Lutathera, 177Lu DOTA-octreotate). However there is a need for additional options for mNET patients. There has been a paradigm shift in anti-cancer therapy over the last decade with the introduction of immunotherapy treatments. Intralesional rose bengal disodium (PV-10) is undergoing clinical development as an oncolytic immunotherapy and is the subject of this phase 1 study examining potential use of PV-10 for treatment of symptomatic mNET of the liver (NCT02693067).
This phase 1 study is evaluating the safety, tolerability and reduction of biochemical markers and symptoms resulting from image guided percutaneous administration of PV-10 in up to 12 participants with mNET of the liver not amenable to resection or other potentially curative therapy. The Target Lesion(s) as defined by the interventional radiologist must be a uni-dimensionally measurable lesion with longest diameter between 1.0cm and 3.9cm as measured. The primary endpoint is safety. Secondary endpoints include objective response rate (ORR), target lesion SSTR and biochemical response. ORR is assessed by contrast enhanced CT and 68Ga-DOTATATE PET standardised uptake value (SUV) allows SSTR expression to be used as a surrogate for tumour viability. In addition to characterizing direct effect of PV-10 in injected lesions, response of uninjected bystander lesions is evaluated by CT and PET to characterize potential systemic benefit. Integration of patient-reported outcome (QLQ-GI.NET21), serum biomarker (CgA) and objective response (PET) data will allow testing of concordance between independent indicators of clinical benefit.
Clinical trial identification
Legal entity responsible for the study
E.A. Wachter, D. Sarson: Employment: Provectus Biopharmaceuticals. All other authors have declared no conflicts of interest.