As many of you will know, Neuroendocrine Cancer UK is a member of INCA (the International Neuroendocrine Cancer Alliance).
INCA is the global voice for patients with Neuroendocrine Cancer, with a mission to raise awareness, push for scientific advancements, focus on identified unmet needs and provide a platform of collaboration for patients to access optimal treatments.
Kate Quirk, a member of our team, sits on the INCA patient panel as a trained Research Advocate, and one of the (many) projects currently under discussion is which clinical trials really matter to the Neuroendocrine Cancer patient community? And which ones are really showing promising results so far?
For anyone with a cancer diagnosis, clinical trials are vital in detecting and treating disease. They look at new ways to try to beat cancer, to extend not only life itself – which is known as Progression Free Survival (PFS), but also Quality of Life (QoL). Most, but not all, patients have QoL as their main goal.
Sometimes the treatments offered can be brand new drugs, and sometimes a combination of drugs which have been shown to be effective in other areas. Sometimes clinical trials can involve using the same drugs but in different ways i.e. increased or reduced dosage, frequency of delivery, or perhaps even the timing, depending on specific outcomes.
Usually, there are 5 stages to clinical trials and it’s only when a drug is tested for the first time in humans, that it actually becomes a Phase 1 Clinical Trial.
Any new drug has to go through a period of discovery and development. Pre-clinical research takes place, even before actual clinical research with much going on behind the scenes that mostly, we never hear about. A new UK drug also has to go through the Medicines and Healthcare Products Regulatory Agency (MHRA) which includes bodies like the General Medical Council (GMC), the General Pharmaceutical Council (GPhC) and the Professional Standards Agency (PSA).
Note: Cancer Research UK provide a full explanation of clinical trial phases here: https://bit.ly/3EuiQdo
And there are other phases after that, for post-market safety monitoring and to check for long term side effects.
So the goal of any clinical trial is to test if a new treatment (or combination) works and is safe.
And all clinical trials should always take into account, Patient Reported Outcomes (PRO’s) and Patient Reported Outcome Measures (PROMS). This can be a vast topic, and one which Neuroendocrine Cancer UK constantly advocate for inclusion at the outset of the design of any new clinical trials.
Kate Quirk spoke to members of our Clinical Advisory panel to gain their views on which are the ‘Trials That Matter’ this year – and what their opinions are on likely outcomes based on what they’re seeing in UK Centres of Excellence.
Note: Many readers may already have taken part in clinical trials, but if you are interested in any of the trials named below, please discuss with your existing Neuroendocrine Cancer clinical team in the first instance. The trials are not listed in any particular order of priority or effectiveness:
SORENTO
A Trial to Assess the Efficacy and Safety of Octreotide Subcutaneous Depot in Patients with GEP-NETS
Dr Tahir Shah, Consultant Transplant Hepatologist
Queen Elizabeth Hospital, Birmingham – NET Centre of Excellence
https://clinicaltrials.gov/ct2/show/NCT05050942
“This is a large randomised clinical trial that will compare standard dose somatostatin analogues [long-acting octreotide 30mg every 4 weeks or long acting Lanreotide 120mg every 4 weeks] versus high dose long-acting octreotide [CAM2029 every 2 weeks].
The new octreotide drug [CAM2029] will provide about 5 times the dose of octreotide as compared to the standard preparations.
There is some evidence that higher than standard doses of somatostatin analogues can have anti-cancer effects such as slower rate of progression. This trial aims to show whether this effect exists and is significant.
The effect of very high levels of octreotide on survival shall also be assessed.
Patients can experience significant side-effects with all these drugs and the clinical trial shall document these also.
Overall, this is a great step in trying to get more out of these extremely useful drugs.”
NETTER-2
Study to Evaluate the Efficacy and Safety of Lutathera in Patients with Grade 2 & Grade 3 Advanced GEP-NET
Dr Amy Eccles, Consultant in Radiology (Nuclear Medicine)
Imperial College Healthcare NHS Trust – NET Centre of Excellence
https://clinicaltrials.gov/ct2/show/NCT03972488
“The aim of NETTER-2 is to determine if Lutathera in combination with long-acting octreotide prolongs progression free survival (PFS) in GEP-NET patients with well differentiated, G2 and G3 tumours.
It draws on the results from NETTER-1 where Lutathera with long-acting octreotide was shown to prolong PFS compared with high-dose, long-acting octreotide alone in G1 and G2 GEP NETs. This is an exciting and important study as it will generate evidence to support the use of Lutathera in G3 GEP NETs.”
Author’s Note – pts with other primary sites have also started to be included in this trial i.e Lung TC and AC.
COMPETE
Efficacy and Safety of 177Lu-Edotreotide PRRT in GEP-NET Patients
Mark Pritchard, Professor of Gastroenterology and Honorary Consultant Gastroenterologist
Royal Liverpool University Hospital – NET Centre of Excellence
https://clinicaltrials.gov/ct2/show/NCT03049189
“When patients with inoperable, metastatic well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs) progress after a first line therapy such as long-acting somatostatin analogues, it is often not currently clear what the most appropriate second line treatment should be. In many patients, treatment options will include Peptide Receptor Radionuclide Therapy (PRRT) and oral targeted drugs such as Everolimus. COMPETE is a prospective, randomised, controlled, open-label, multi-centre Phase III trial comparing responses to 177Lu-Edotreotide PRRT and Everolimus in patients with inoperable, progressive, somatostatin receptor-positive (SSTR+) GEP-NETs. Recruitment of 309 patients has been completed and these participants are currently being followed up to see how they have responded. The results of this trial should be available in a few years.”
COMPOSE (ITM Follow-on)
Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-Differentiated Aggressive Grade 2 and Grade 3 GEP-NETs
Dr Raj Srirajaskanthan, Consultant Gastroenterologist
Kings College Hospital NHS Foundation Trust – NET Centre of Excellence
https://clinicaltrials.gov/ct2/show/NCT04919226
“This is a very important study to help us determine the role of PRRT in patients with well differentiated Grade 2 and 3 NETs. Currently, PRRT is not licenced for Grade 3 NETs. However, there is evidence to suggest it may be effective. This study is a randomised trial assessing PRRT with up to 6 cycles of PRRT vs A Best Supportive Care arm. The BSC arm is chosen by the clinician in charge of patients care and includes Everolimus or chemotherapy. The chemotherapy regimens are the ones currently used in clinical practice. This study hopefully will be able to determine if PRRT is suitable for patients with Grade 2 and Grade 3 NETS and also how effective it can be compared to standard therapies.”
SEQTOR
Efficacy and Safety of Everolimus + 5FU Given One Upfront, the Other Upon Progression in Advanced PNETs
Juan Valle, Professor of Medical Oncology and Chair of the National Cancer Research Institute NET Subgroup
The Christie NHS Foundation Trust, Manchester – NET Centre of Excellence
https://clinicaltrials.gov/ct2/show/NCT02246127
“In this study, patients with well-differentiated pancreatic neuroendocrine tumours were randomly allocated to one of two groups: one group start with chemotherapy (Streptozocin/5FU) for as long as effective and then crossing over to Everolimus on disease progression (worsening); the other group started with Everolimus and changed to chemotherapy (i.e. the reverse order). The results of the study were presented at the 2022 ESMO (European Society for Medical Oncology) Congress. In summary, there was no difference in the time it took the cancer to get worse (progression-free survival; which was the primary endpoint of the study) from starting the first treatment (either chemotherapy or Everolimus). Not surprisingly, patients receiving chemotherapy were observed to have a greater degree of tumour reduction (higher response rate). Therefore, chemotherapy may be considered if tumour reduction is important (for example, if considering surgery or aim to reduce tumour bulk which may be causing symptoms), but otherwise, the order of treatment does not matter.”
ASPEN
A Prospective Evaluation of the Management of Sporadic, Asymptomatic Non-Functioning Small PNETs
Juan Valle, Professor of Medical Oncology and Chair of the National Cancer Research Institute NET Subgroup
The Christie NHS Foundation Trust, Manchester – NET Centre of Excellence
https://clinicaltrials.gov/ct2/show/NCT03084770
“Small (less than 2cm in size) non-functioning pancreatic NETs have, for a long time, created debate about whether they should be operated on or not (sometimes known as watch-and-wait). Once they reach 2 cm, surgery is offered. In the ASPEN study, patients with such pancreatic NETs less than 2cm are actively followed up to understand how they evolve (if at all) over time; the study is also evaluating patient-reported quality of life (QoL). This important observational study will inform how we make decisions about these small NETs in the future.”
Additional:
One other Clinical Trial of note in the USA is considered to be CABINET:
Testing Cabozantinib in Patients with Advanced Pancreatic Neuroendocrine AND Carcinoid Tumours
However, at the time of writing, CABINET is not currently recruiting in the UK:
https://clinicaltrials.gov/ct2/show/NCT03375320
There are several Clinical Trial databases available, and some professional societies and charities – such as Neuroendocrine Cancer UK – that may provide information on trials currently being run in the UK.
Keep an eye on this page to find out the latest trials on offer.
In addition, the Neuroendocrine Cancer UK Clinical Expert Advisory Panel is a group of specialists from surgeons to dieticians, who all have a wealth of experience working with Neuroendocrine Tumours.
The advisors are on hand to answer any of your queries that you can’t find an answer for immediately. Please take a look here for more information on the panel.
END