The UK, through the National Cancer Research Institute (NCRI) Neuroendocrine Subgroup, is able to offer access to clinical trials to patients diagnosed with neuroendocrine tumours. It is important to note that the term “neuroendocrine tumours” refers to many types of NETs and clinical trials are tailored to address a specific scientific question within a particular type, stage and activity of NET. Therefore an individual patient may be eligible for one or more trials at a time, or none.
If you wish to see the portfolio map of clinical trials in NETs, please follow the NCRI link: http://csg.ncri.org.uk/portfolio/portfolio-maps/ and select “Upper gastro-intestinal cancer” where you will find “Map B – Neuroendocrine”
Follow the NCRI link given for each study for more details of the clinical trial (including inclusion and exclusion criteria) and contact details. Where available, links to the clinicaltrials.gov database are also provided.
Open studies (in alphabetical order)
ARTISAN | UK CI: Dr Rohini Sharma
This is an open label phase II study for patients with inoperable metastatic neuroendocrine liver deposits to see whether treatment with Selective Internal Radiation Therapy (TheraSpheres) could lead to improved treatment response rates with acceptable toxicity (minimal serious adverse events reported). This research will also look at the progression free survival and quality of life of the patients who enroll in the study.
Lead Site: Imperial College Hospital, London
Study Opened: April 2020
NET-02 | UK CI: Dr Mairead McNamara (Christie, Manchester)
A multi-centre, randomised, parallel group, open-label, phase II, single-stage selection trial of liposomal irinotecan (nal-IRI) and 5-fluorouracil (5-FU)/folinic acid or single agent docetaxel as second-line therapy in patients with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma (NEC)
Inclusion Criteria:
•Histologically-confirmed poorly differentiated extra-pulmonary NEC (G3)
•Prior treatment with first-line platinum-based chemotherapy
•ECOG performance status ≤2
•Radiological evidence of disease progression OR discontinuation of first-line platinum-based chemotherapy due to intolerance
•Tumour Ki-67 > 20%
Sites: Manchester, Edinburgh, Newcastle, Sheffield, Leeds, Guys & St Thomas’, Imperial College, Royal Free, Royal Marsden, Southampton, Cardiff, Coventry & Warwick, Clatterbridge, Belfast, Birmingham, Glasgow.
NETTER-2 | UK CI: Dr Raj Srirajaskanthan (Kings)
A phase III multi-center, randomized, open-label study to evaluate the efficacy and safety of Lutathera in patients with Grade 2 and Grade 3 advanced GEP-NET. The aim of NETTER-2 is to determine if Lutathera in combination with long-acting octreotide prolongs PFS in GEP-NET patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naive patients are eligible, as well as patients previously treated with SSAs in the absence of progression.
Primary end-point is rate of PFS through 72 weeks.
Participating sites: Kings College Hospital; Bristol Oncology Centre; Weston Park Hospital, Sheffield; Liverpool, Royal Free Hospital; Guys and St Thomas’, London.
Main trial participation criteria:
Inclusion:
1. Metastatic /locally advanced, inoperable (curative intent) histologically proven, well differentiated Grade 2 or Grade 3 gastroenteropancreatic neuroendocrine (GEP-NET) tumor diagnosed within 6 months prior to screening.
2. Ki67 index ≥ 10 and ≤ 55%.
3. Patients ≥ 15 years of age and a body weight of > 40kg at screening.
4. All target lesions (documented by CT/MRI) SSTR receptor positive as assessed by Octreotide scan or Ga68-PET scan. Target lesion uptake must be > normal liver uptake (Krenning 3 or 4)
5. Karnofsky Performance Score (KPS) ≥ 60.
6. Presence of at least 1 measurable site of disease.
Exclusion:
1. Creatinine clearance < 40 mL/min.
2. Hb <8.0 g/dL; WBC < 2 x 109/L; platelets < 75 x 109/L.
3. Total bilirubin > 3 x ULN. Serum albumin < 3.0 g/dL
4. Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the study.
5. Documented RECIST progression to previous treatments for the current GEP-NET at any time prior to randomization.
6. Previous therapy with Interferons, Everolimus (mTOR-inhibitors), chemotherapy or other systemic therapies administered for more than 1 month and within 12 weeks prior to randomization in the study.
7. Previous radioembolization, chemoembolization and radiofrequency ablation.
8. Surgery within 12 weeks prior to randomization in the study.
COMPETE | UK CI: Dr Navalkisoor (Royal Free Hospital)
A prospective, randomised, Controlled, Open-label, Multicentre phase III study to evaluate efficacy and safety of Peptide Receptor Radionuclide Therapy (PRRT) with Lutetium 177-Edotreotide compared to targeted molecular therapy with Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+), neuroendocrine tumours of gastroenteric or pancreatic origin (GEP-NET).
Participating Sites: Royal Free Hospital, Kings College Hospital, ? Beatson Cancer Centre, Glasgow; ? Christie Hospital, Manchester; ? Queen Elizabeth Hospital; Birmingham
Main Inclusion/Exclusion Criteria:
Inclusion:
1.Histologically confirmed well-differentiated non-functional gastrointestinal neuroendocrine tumour or functional/non-functional pancreatic neuroendocrine tumour, grade G1 or G2 (Ki-67 < 20%), unresectable or metastatic.
2. Availability of existing biopsy specimen from primary tumour or metastasis or, if unavailable, willingness to undergo current biopsy for secondary central analysis.
3. Measurable disease per RECIST 1.1, on CT/MRI scans.
4. Somatostatin receptor positive (SSTR+) disease, as evidenced by octreotide or Ga68 PET scan SSTR imaging (SRI) within 4months prior to randomization. All target lesions and > = 90% of non-target lesions need to be positive for SSTR.
5. Radiological disease progression within the 12 months prior to randomisation.
6. Karnofsky performance status (KPS) scale > = 70.
7. Glomerular filtration rate (GFR, MDRD) > = 60 mL/min/1.73 m2.
Exclusion:
1. Known hypersensitivity to edotreotide or everolimus.
2. Known hypersensitivity to DOTA, lutetium-177, or any excipient of edotreotide or everolimus.
3. Prior exposure to any peptide receptor radionuclide therapy (PRRT), including 177Lu-edotreotide, 90Y-edotreotide or other SSTR-targeting agents (e.g. 177Lu-octreotate or high-dose 111In-pentetreotide).
4. Prior therapy with mTor inhibitors.
5. Prior EFR (extended field radiation) to GEP-NET lesions or radioembolisation therapy (e.g. 90Y microspheres, 131I-lipiodol) with administration to the liver.
6. Total hepatic tumour burden > 70%.
Recent trials
ADIUVO – closed to recruitment
CLARINET FORTE – closed to recruitment and result presented / published
IMMUNET – closed to recruitment
PDR-001 – closed to recruitment
PEN221 – recruitment complete
REMINET – closed to recruitment
SEQTOR – closed to recruitment
FETONET – closed
SPINET – recruitment completed
ADUIVO | UK PI Wiebke Arlt [NCRI link][NCT00777244]
Efficacy of Adjuvant Mitotane Treatment in Prolonging Recurrence-free Survival in Patients With Adrenocortical Carcinoma at Low-intermediate Risk of Recurrence
This is an international study involving the USA, Canada, France, Germany, Italy, Netherlands and the UK. It is evaluating the effectiveness of a chemotherapy drug called mitotane in reducing the chances of disease relapse after patients have had potentially-curative surgery of adrenal cancer (adrenocortical carcinoma).
Recruiting UK site: Queen Elizabeth Medical Centre, Birmingham
CLARINET-Forte | UK PI Christos Toumpanakis [NCRI link][NCT02651987]
Efficacy and safety of Lanreotide Autogel 120 mg administered every 14 days in well-differentiated, metastatic or locally-advanced, unresectable pancreatic or midgut neuroendocrine tumours, having progressed radiologically while previously treated with Lanreotide Autogel 120 mg administered every 28 days
A previous study (CLARINET) has shown that lanreotide, given every 4 weeks, delays the growth of neuroendocrine tumours of the pancreas or mid-gut. In time, the tumours will get larger; this study is evaluating how effective lanreotide is when the injection interval is then reduced to 2-weekly (i.e. two injections per month, instead on once a month) in such patients.
Recruiting UK sites: Queen Elizabeth Medical Centre, Birmingham; Royal Free Hospital, London; and The Christie, Manchester
FETONET | UK CI Rohini Sharma [NCRI ID 15548]
Evaluation of [ 18 F]fluoroethyl triazole labelled [Tyr 3 ]Octreotate analogue for the imaging of Neuroendocrine tumours
The use of nuclear imaging is well-established in patients with NETs; octreotide scans and 68-Gallium PET scans are most commonly used. In this study, a novel tracer is being evalu- ated called [18F]fluoroethyl triazole labelled [Tyr3]Octreotate analogue ([18F]-FET-βAG- TOCA, for short). At this stage, this novel tracer does not replace the standard scans.
Recruiting UK sites: Imperial College, London
IMMUNET | UK CI Tim Meyer [NCRI link]
Systematic Evaluation of the Immune Environment of Neuroendocrine Tumours
This clinical trial is investigating how the immune system responds to neuroendocrine cancers and aims to provide a scientific rationale that will lead to clinical trials of immunotherapy in this group of patients. The study is open for patients with NETs due to commence systemic therapy (either for advanced disease or prior to potential surgery); fresh tissue biopsy and blood samples to characterise the diversity, quantity and quality of the immune cells infiltrating the NET.
Recruiting UK sites: Royal Free Hospital, London; Kings College, London; and The Christie, Manchester
PDR001| UK PI Chrissie Thirlwell
Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)
This study is evaluating the immunotherapy drug PDR001 which blocks PD-1. The study is open for selected neuroendocrine tumours.
Recruiting sites: The Beatson, Glasgow and Royal Free, London
PEN-221 | UK PI Tim Meyer [NCT02936323]
PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers
This is first-in-human trial run in the UK and USA evaluating a new drug which is made of a somatostatin like peptide conjugated to the cytotoxic drug mertansine (DM1). The recommended dose has now been defined and the drug is being tested in pancreatic and midgut NET as well as small cell lung cancer.
Recruiting sites: UCLH, London and The Christie, Manchester
REMINET | UK PI Juan Valle [NCRI link][NCT02288377]
A European, multicentre, phase II/III randomised double-blind, placebo controlled study evaluating Lanreotide as maintenance therapy in patients with non-resectable duodeno-pancreatic neuroendocrine tumours after first-line treatment
This is an academic study led by colleagues in France assessing the effectiveness of lanreotide injections as a holding treatment (“maintenance”) following initial treatment (which may be either chemotherapy or a targeted-therapy, such as everolimus or sunitinib) in patients with well-differentiated neuroendocrine tumours of the pancreas or duodenum. Patients are randomised to receive either lanreotide or placebo.
Recruiting UK sites: Royal Free, London & The Christie, Manchester
SEQTOR | UK PI Tim Meyer [NCRI link][NCT02246127]
Randomized phase III open label cross-over study to compare the efficacy and safety of everolimus followed by chemotherapy with STZ-5FU upon progression or the reverse sequence, chemotherapy with STZ-5FU followed by everolimus upon progression, in advanced progressive pNETs.
In this academic, ENETS-approved study, sponsored by the Spanish neuroendocrine group (GETNE) patients with well-differentiated pancreatic neuroendocrine tumours (pNETs) receive treatment with chemotherapy (streptozocin and 5-FU) and everolimus, one after the other. In the trial patients are allocated (at random, by chance) to either receive everolimus first (then chemotherapy) or chemotherapy first (then everolimus). The aim of the study is to evaluate whether there is a difference in outcome depending on the sequence of treatment.
SPINET | UK PI Martyn Caplin [NCT02683941]
Efficacy and Safety of Lanreotide Autogel/ Depot 120 mg vs. Placebo in Subjects With Lung Neuroendocrine Tumors (SPINET)
This is an international Phase 3, prospective, multi-center, randomized, double-blind, study evaluating the efficacy and safety of lanreotide plus best-supportive care (BSC) versus placebo plus BSC for the treatment of well-differentiated, metastatic and/or unresectable, typical or atypical lung NETs.
Recruiting sites: The Beatson, Glasgow, Royal Surrey, Guilford, Royal Free, London, Kings College, London, The Christie, Manchester, The Churchill, Oxford.
