CONTROL NETS

The aim of the CONTROL NETS trial is to find the optimal treatment to improve disease control in patients with advanced Neuroendocrine tumours (NETs).

Neuroendocrine tumours (NET) are rare cancers that can occur in different locations in the body, including the gastro-intestinal tract and the pancreas.  The purpose of  CONTROL NETs is to determine the activity of capecitabine plus temozolomide (CAPTEM)/peptide receptor radionuclide therapy (PRRT) in combination, in both pancreatic neuroendocrine tumours (pNETS) and mid-gut (small bowel) neuroendocrine tumours (mNETS) patients.

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Trial Status

In Follow-up

Cancer Type

NeuroEndocrine Tumours (NETs)

AIM

The aim of the CONTROL NETS trial is to find the optimal treatment to improve disease control in patients with advanced Neuroendocrine tumours (NETs). More specifically, the purpose of the study is to determine the activity of capecitabine plus temozolomide (CAPTEM)/peptide receptor radionuclide therapy (PRRT) in combination, in both pancreatic neuroendocrine tumours (pNETS) and mid-gut (small bowel) neuroendocrine tumours (mNETS) patients.

SUMMARY

Neuroendocrine tumours (NET) are rare cancers that can occur in different locations in the body, including the gastro-intestinal tract and the pancreas. The cancer begins in neuroendocrine cells, which are cells that produce hormones that help control normal body function. NETs that have spread around the body (metastasised), or cannot be removed by surgery, are incurable using currently available treatments. Survival can be long for some patients, depending on the growth rate of the cancer cells and differs between NETs of different locations of origin in the body. Although NETs are rare in terms of the number of new cases each year, the total number of patients with NETs in Australia at any given time is much more substantial, thus impacting on the community.

Current standard therapies for advanced NETs include chemotherapy, targeted therapy, hormone treatment and radioactive (“radiopeptide”, LuTate) treatments to help manage the symptoms and control tumour growth and spread. Many patients will need to use more than one of these types of treatments for their cancer. However, there are still many questions about the best way of using these, and newer treatments, to help patients.

CONTROL NETS will study the best use of chemotherapy and radiopeptide treatment in combination to help improve tumour control in small bowel and pancreatic NETS. The effectiveness of combining chemotherapy (CAPTEM) and radiotherapy treatment (LuTate) will be compared with a reference standard therapy (LuTate alone in small bowel NETs) and CAPTEM chemotherapy alone in pancreatic NETs.

Eligible patients with advanced pancreatic or small bowel NET will be entered into their respective study (by tumour type) then randomized to receive either CAPTEM/LuTate combination or LuTate alone in small bowel NETs, or CAPTEM chemotherapy alone in pancreatic NETs . The study treatment will be given over 32 weeks, with 12 months follow up for pancreatic NETs and 24 months follow up for small bowel NETs.

If the study results show that the combination therapy has a positive effect, it would then be further investigated in a larger Phase III trial. This has the potential to influence future treatment of patients with advanced small bowel or pancreatic NETS.

Participating Centres

New South Wales
Royal North Shore Hospital
St George Hospital
Queensland
Royal Brisbane and Womens Hospital
Victoria
Peter MacCallum Cancer Centre
Western Australia
Fiona Stanley Hospital

Trial Status

In Follow-up

Cancer Type

NeuroEndocrine Tumours (NETs)

Protocol Title

“Capecitabine ON Temozolomide Radionuclide therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study”

Publication Reference

None to date

Conference Presentation Reference

None to date

Aim

The aim of CONTROL NETS is to find the optimal treatment to improve disease control in patients with advanced NETs. More specifically, the purpose of the study is to determine the activity of capecitabine plus temozolomide (CAPTEM)/peptide receptor radionuclide therapy (PRRT), in combination, in both pancreatic neuroendocrine tumours (pNETS) and mid-gut (small bowel) neuroendocrine tumours (mNETS) patients.

Background

Neuroendocrine tumours (NETs) that have metastasised or cannot be removed by surgery are incurable with currently available treatments. Standard therapies to help manage advanced NET and to improve survival in patients include chemotherapy, hormone treatment and radioactive (“radiopeptide”) treatments to help with the numerous and varies symptoms. Many patients will need to use more than one of these types of treatments for their cancer. However, there are still many questions about the best way of using these, and newer treatments, to help patients, particularly as some treatments have only been studied in small groups of patients.

CONTROL NETs aims to assess whether the combination of chemotherapy with CAPTEM, combined with radiopeptide treatment  (PRRT: LuTate) evaluated in parallel in small bowel and pancreatic NETs, has sufficient activity to be subsequently explored in a Phase III trial. A control reference arm will be  used in each tumour group as a calibration arm to ensure the assumptions, upon which the statistical plan is based, were accurate. These control arms are: CAPTEM alone (in pancreatic NET group) and LuTate alone (in mid-gut NET group).

All the treatments used in this trial have been looked at before in earlier trials. They have shown activity against this type of cancer but there is no comparative data.

The results will also help inform the design of larger, future clinical trials aimed at determining the best treatment for these diseases.

CLINICAL TRIAL DESIGN

CONTROL NETS is a Phase II, randomised, parallel group,  multicentre trial.

Eligible participants will be entered into their respective study (by tumour type) then randomized to receive

  1. CAPTEM/LuTate combination or CAPTEM chemotherapy alone (pancreatic NETs)
  2. CAPTEM/LuTate combination or LuTate alone (small bowel NETs).

Combination chemotherapy (CAPTEM) involves taking 2 different types of tablets – capecitabine, given twice a day for 14 days, and temozolomide, given daily for 5 days – every 4 weeks. This treatment continues for 6 to 8 cycles (about 5 to 7 months). Patients who are randomised to chemotherapy alone and then have progressive disease will be able to access the radiopeptide treatment at that time.

Radiopeptide treatment (LuTate) involves receiving treatment intravenously once every 8 weeks, for a total of 4 treatments (about 6 months). Patients are given fluids through the drip as well for 4 hours to help protect their kidneys from any potential damage.

Patients in the CAPTEM chemotherapy plus LuTate arm will receive the same radiopeptide treatment, plus the combination chemotherapy every 8 weeks. 4 cycles will be given in total (about 6 months).

Treatment for all groups will continue for 32 weeks. Study participants will be required to visit the clinic, between 9 to 12 times during the treatment stage, depending on which treatment they receive. The visits will vary in length between 2 and 6 hours.

Afterwards, there will be 12 months of follow-up for pancreatic neuroendocrine tumour patients and 24 months for small bowel neuroendocrine tumour patients.

Participating Centres

New South Wales
Royal North Shore Hospital
St George Hospital
Queensland
Royal Brisbane and Womens Hospital
Victoria
Peter MacCallum Cancer Centre
Western Australia
Fiona Stanley Hospital

Study Chairs

Associate Prof. Nick Pavlakis (Royal North Shore Hospital, St Leonards NSW)
Prof. J Harvey Turner (Fremantle Hospital, The University of WA, Freemantle WA)

Principal Investigator

Associate Prof. Nick Pavlakis

More Information

Available online at the Australian New Zealand Clinical Trial Registry (ANZCTR) here

Funding

Unicorn Foundation