ArTisaN
Research type
Research Study
Full title
A Phase II Assessment of the Safety and Efficacy of TheraSphere® Selective Internal Radiation Therapy (SIRT) in the treatment of Metastatic (Liver) Neuroendocrine Tumours (NETs).
IRAS ID
231087
Contact name
R Sharma
Contact email
Sponsor organisation
Imperial College London
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
This prospective, open label, single centre Phase 2 study will be performed in patients with inoperable metastatic neuroendocrine liver deposits to test the hypothesis that treatment with Selective Internal Radiation Therapy (Theraspheres) will lead in improved treatment response rates with acceptable toxicity. Secondary aims are the assessment of Progression Free Survival and Quality of Life. Translational end points are the assessment of Radiomics in prediction treatment response.
Lay summary of study results: From February 2019 to November 2022, 29 patients agreed to participate in a clinical trial. However, after initial checks, five of these patients didn’t meet the necessary criteria, one withdrew consent, and two passed away from their illness before receiving treatment. This left 21 patients who completed week 8 assessment and were included in the per protocol analysis.
The average age of the patients was 63, and most had cancer that started in the small bowel (48%). The majority had moderately severe disease, and about a third had cancer that had spread beyond the liver. Patients were heavily pre-treated, with eleven (52%) having at least two previous lines of systemic therapy, including seven patients who had received PPRT prior to SIRT. Two patients had tumors that caused symptoms managed by specific medication.
At the 8-week check, 21 patients were assessed to see how their cancer responded to the treatment. The Primary outcomes: Objective response rate within the treated liver was 14% (n=3) using RECIST 1.1, and 45% (n=9) according to mRECIST. At 8 weeks, 71% of patients had stable disease. At 3 months, 17 patients were evaluated for response assessment. One patient withdrew from the trial. ORR using RECIST 1.1 was 10%, whilst using mRECIST, ORR was 44%. At 6 months,12 patients were assessed for response. Due to Covid-19, 2 patients were unable to return for 6 monthly imagine and 2 patients underwent MRI imaging such that mRECIST assessment was not possible. ORR at 6months according to RECIST 1.1 was 8% and mRECIST was 20%. We then considered both overall and liver specific Progression Free Survival (PFS). The median hepatic PFS was consideriable longer than PFS: 48.1months compared with median PFS was 13.3months suggesting that SIRT resulted in good control of hepatic disease.
Regarding safety, 21 patients were monitored for side effects over 6 months. The most common mild side effects were fatigue (13 patients, 63%) and abdominal pain (9 patients, 43%). Two patients (10%) experienced more serious liver-related issues, which improved with treatment. Some patients also had temporary decreases in white blood cells, but there were no severe or long-lasting laboratory abnormalities. Importantly, none of the patients developed symptoms related to hormone levels after treatment.
Quality of life was also assessed. There was a slight dip in overall health at 8 weeks and 3 months, but it returned to baseline by 6 months. There were no major changes in physical, emotional, or social functioning, and no worsening of symptoms related to their cancer after treatment. Fatigue was the most reported symptom, but it didn’t significantly worsen over time.
A further analysis looked at patients who had received a previous treatment (called [177Lu]Lu-DOTA-TATE) before joining the trial. These patients did not experience additional severe side effects from the combination of treatments. Their cancer remained stable or improved slightly in response to the treatment during the trial.
Overall, the study suggests that the treatment provided good control of liver-specific cancer and was generally well-tolerated by patients.
REC name
London - Bloomsbury Research Ethics Committee
REC reference
18/LO/0761
Date of REC Opinion
26 Jun 2018
REC opinion
Further Information Favourable Opinion