AGITG Trial Updates December 2019

NEO-CREATE becomes the second AGITG Endorsed Study

The pilot study NEO-CREATE has become the second AGITG Endorsed Study, led by study chair Dr Amitesh Roy.

“NEO-CREATE is a feasibility study with a safety lead-in investigating the role of immunotherapy in conjunction with chemotherapy and radiotherapy in the early stage of oesophagus and gastro-oesophageal junction cancers,” says Dr Roy.

NEO-CREATE aims to assess the safety of adding the immunotherapy drug avelumab to chemo-radiation using two standard chemotherapy drugs, carboplatin and paclitaxel, before surgery in patients with cancers of the oesophagus or the gastro-oesophageal junction.

According to the current standard of care, chemoradiotherapy treatment is given to patients before surgery. As well as assessing the safety, tolerability and feasibility of the treatment, researchers want to establish primary efficacy by way of looking at the effect of immunotherapy on the tumour by analysing the tumour sample after the surgery.

“The idea for AGITG to create the Endorsed Study Model was to proactively engage with the investigators conducting pilot trials, for example, and those trials which are possibly sponsored by the local institutions but not by AGITG,” says Dr Roy.

NEO-CREATE is currently recruiting patients.

First patient joins PALEO

The first participant has joined the phase II PALEO trial, which is investigating palliative oesophageal cancer chemoradioimmunotherapy.

The PALEO team, led by Dr Fiona Day, is studying the effects of nivolumab and SBRT added to chemoradiotherapy in metastatic oesophageal cancer. It aims to prolong relief from dysphagia (difficulty swallowing) for patients undergoing palliative treatment for oesophageal or gastro-oesophageal cancer.

“PALEO offers multimodality treatment to address the complications of oesophageal cancer,” says Dr Day. “Each of the treatment components is typically well tolerated, which fits our aim of optimising patient quality of life by aiding return to a normal diet with minimal side effects. The feasibility of this approach is demonstrated by recruitment of our first patient shortly after trial opening.”

Typically, patients with oesophageal cancer present with dysphagia. Dr Day and Prof Martin found that first line concurrent chemoradiotherapy with low dose weekly carboplatin and paclitaxel resulted in all 18/ patients in a phase I study achieving improvement in their dysphagia. The majority of patients also returned to a normal diet, and at least three achieved complete relief of their dysphagia for over a year.

In the PALEO study, researchers aim to prolong this dysphagia relief and simultaneously  provide distant disease control with the use of immunotherapy and SBRT to a metastatic site.

PALEO is open in Calvary Mater Newcastle and recruiting patients with oligometastatic oesophageal or gastro-oesophageal cancer. It is the first trial to be activated under the AGITG Endorsed Study Model.

Find out more about PALEO here.

First two sites open for MASTERPLAN

The MASTERPLAN trial for pancreatic cancer patients has opened its first site at Princess Alexandra Hospital, Queensland, and Royal Adelaide Hospital, South Australia.

MASTERPLAN is a randomised, phase II study of mFOLFIRINOX with and without stereotactic radiotherapy (SBRT) for pancreatic cancer patients with high risk and locally advanced disease. It aims to determine if adding SBRT to chemotherapy will improve locoregional control for patients with high-risk, borderline resectable, locally advanced pancreas cancer.

Approximately half of all pancreatic cancer patients experience locoregional recurrence. Even with surgery, 40% of patients will experience a localised regional recurrence in the first 12 months.

SBRT allows a significant dose escalation compared to standard external beam radiotherapy (EBRT) without an increase in toxicity. This is anticipated to increase the number of tumour cells killed and reduce rates of locoregional recurrence.

“There is a desperate need for improved treatment for patients with pancreatic cancer,” says Dr Andrew Oar, the Study Chair. “We hope that this study investigating the combination of cutting edge radiotherapy with highly active chemotherapy will significantly improve patient outcomes in this devastating disease.”

The study aims to recruit 120 patients across Australia with more sites expected to open soon.

Find out more about MASTERPLAN here.


New Study Chair for NABNEC

Dr Lorraine Chantrill will assume the role of NABNEC Study Chair, following the departure of Associate Professor Mustafa Khasraw.

Associate Professor Khasraw, who has led the study since it opened in 2016, is taking up a new position as Deputy Director of Duke University’s Center for Cancer Immunotherapy.

Dr Chantrill is the Chair of the AGITG Upper GI Working Party, and will lead NABNEC until study closure. NABNEC is a randomised phase II trial of patients with grade 3 neuroendocrine carcinomas (NECs). It aims to determine the safety and efficacy of carboplatin plus nab-paclitaxel in comparison with carboplatin plus etoposide.

The study is open in all six states across Australia. Thirty-five participants have joined the study out of a target of 70.

Find out more about NABNEC here.


MODULATE reaches over 75% of its recruitment target

The MODULATE study, led by Prof Niall Tebbutt, is investigating the effectiveness, safety and tolerability of the immunotherapy treatment nivolumab with either BBI-608 or BNC105 for patients with metastatic colorectal cancer – an experimental strategy aiming to stimulate the immune system to attack the cancer.

On the significance of the study, Prof Tebbutt says, ‘This is an important and exciting study for the group as it is represents the first study of immunotherapy undertaken by AGITG.’

Nivolumab is an antibody (a type of human protein) that can stimulate the immune cells (called lymphocytes) to attack a cancer. This process is known as “immunotherapy”. Nivolumab acts against PD-1 which is a protein in cancers that researchers believe allows cancer to escape the immune system. Nivolumab can stop the cancer cells escaping the immune system and the body’s own immune reaction may help to destroy cancer cells.

In order for nivolumab to be effective, immune cells need to infiltrate close to the tumour itself. It has been observed that in many cases of bowel cancer, immune cells do not penetrate near the tumour which may explain why nivolumab given on its own is an ineffective treatment for many patients with bowel cancer. This does not apply to a number of other cancer types.

BBI-608 is a molecule that inhibits cancer stem cells, and particularly the signalling protein STAT3. STAT3 suppresses the immune system and inhibits immune cells getting close to tumour cells. Researchers believe that BBI-608 will allow immune cells to move close to tumour cells and stimulate the immune cells in combination with nivolumab.

The other treatment arm being studied is BNC105, a ‘vascular disrupting agent’. This damages the blood supply of tumour, resulting in tumour damage and inflammation. Researchers believe this could allow immune cells to move close to the tumour and, in combination with nivolumab, stimulate the immune cells.

This study has recruited 76 out of a total of 90 participants since its opening in September 2018, and it is expected recruitment will be completed by early 2020.

Find out more about MODULATE here.