• CONTROL NETS

Trial Status

In Follow-up

Cancer Type

NeuroEndocrine Tumours (NETs)

Protocol Title

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

Purpose of the Study

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.

Eligibility Criteria

Inclusion Criteria

  1. Adults greater than or equal to 18 years old with histologically proven pancreatic or midgut NETs
  2. The presence of somatostatin receptor avidity suitable for PRRT demonstrated on 68Ga-octreotate PET scan;
  3. Ability to swallow oral medication;
  4. Adequate renal function
  5. Adequate liver function
  6. Life expectancy of at least 9 months;
  7. Study treatment both planned and able to start within 28 days of randomisation
  8. Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments;
  9. Signed, written informed consent.

Exclusion Criteria

  1. Primary NETs other than small bowel (midgut) or pancreatic NETs;
  2. Prior Peptide Receptor Radionuclide Therapy;
  3. Major surgery/surgical therapy for any cause within one month;
  4. Poorly controlled concurrent medical illness. E.g. unstable diabetes
  5. History of other malignancies within 5 years except where treated with curative intent AND with no current evidence of disease AND considered not to be at risk of future recurrence
  6. Any uncontrolled known active infection, including chronic active hepatitis B, hepatitis C, or HIV.
  7. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule, including alcohol dependence or drug abuse;
  8. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

DETAILED INFORMATION AVAILABLE ON

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

PRINCIPAL INVESTIGATOR

A/Prof Nick Pavlakis

FUNDING

Unicorn Foundation

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

Principal Investigator

Associate Prof. Nick Pavlakis

More Information

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

Funding

Unicorn Foundation