Our impact - GI Cancer Trials

Since 1991, we have been working towards a better future for people with GI cancer. We are proud that our collaborative, patient-centred research has been integral to worldwide changes in medical practice. Our clinical trials have improved outcomes for people with GI cancer and provided access to cutting-edge treatments and high care support not otherwise available.

Our research has made a lasting impact on how GI cancers are treated, both in Australia and around the world.

Driven global changes in medical practice for oesophageal, colorectal, and gastrointestinal stromal tumour (GIST) cancers.
Led pioneering clinical trials in stomach, rectal, anal, and pancreatic cancers.
Provided patients with early access to cutting-edge treatments and high-quality care not otherwise available.
Established national surgical guidelines to improve outcomes for pancreatic cancer patients.

Survival outcomes have improved through research that has tested:

Oral chemotherapy as an alternative to intravenous therapies
New and emerging drug treatments.
Targeted and personalised therapies.
Preoperative chemoradiation.
Innovative treatment combinations.

Quality of life has been enhanced by:

Reducing side effects through new chemotherapy combinations.
Identifying which patients are unlikely to benefit from certain therapies.
Showing that shorter treatment durations can be just as effective, with fewer side effects, for colorectal cancer.

Targeted therapies have advanced through findings that:

Demonstrating that a tumour growth–inhibiting drug is safe and active in oesophageal cancer.
Showing that a monoclonal antibody may benefit selected patients with bile duct cancer.

Impact spotlights on trial achievements

CO.17: A breakthrough in advanced colorectal cancer treatment

In the early 1990s, there was only one treatment available for advanced colorectal, or bowel cancer, the chemotherapy drug 5-fluoracil. At GI Cancer Trials and around the world, researchers knew there was a need for more options for patients, especially because bowel cancer affected 9,662 people every year and its incidence was growing. Continue reading

GAP: A small trial that made a big difference for people with pancreatic cancer

The GAP study challenged the prevailing standard treatment for pancreas cancer – patients that were considered curable had surgery first, followed by chemotherapy. While the standard treatment was considered effective for patients that are able to complete chemotherapy, a significant proportion of patients are not able to complete it. Continue reading

ICECREAM: Adding crucial data to the complex colorectal treatment jigsaw

If diagnosed early, colorectal cancer is one of the most treatable forms of cancer, but once it is advanced there are often few effective treatment options available. Research has shown that patients with a rare genetic mutation called G13D may respond to treatment differently and the ICECREAM trial aimed to find out more. Continue reading

INTEGRATE and INTEGRATE II/b: Improving survival for people with stomach cancer

Clinical trials are constantly evolving as new insights come to light and the INTEGRATE studies are a prime example of this. Finding a better treatment for stomach cancer patients is crucial; worldwide, it is the fifth most common cancer and the sixth leading cause of cancer deaths. Continue reading

View the results of our completed trials

ABC
ACTICCA-1
Advanced GIST/ EORTC 62005
Adjuvant GIST/ EORTC 62024
AG0001H
AG9401
AG9601
AG9801
ALaCaRT
ALT-GIST
ASCOLT
ATTACHE
ATTAX
ATTAX 2
ATTAX-3
CO.17
CO.20
CO.23
CONTROL NETs
DaVINCI
DECO
DOCTOR
EORTC 40983
ESPAC-3
FORECAST-1
GAP

GENESCREEN
GOFURTGO
ICECREAM
IG9401
IMPACT
INTEGRATE
INTEGRATE-IIa
INTEGRATE-IIb
InterAACT
LAP07
MAGIC
MAX
MODULATE
MONARCC
NSABP CO6
NSABP CO-7
PA.3
PA.7
PAN 1
PETACC-6
QUASAR 2
REGISTER
RoLaCART
SCOT
SPAR
SUPER
TACTIC
TOPGEAR
TROG 01.04 / IG0103R

Clinical Study Results

REGISTER – clinical trial – Phase II study of risk evaluation in gastro-intestinal stromal tumour (GIST) with selective therapy escalation for response

The REGISTER study aimed to evaluate the time to ultimate disease progression in patients with exon 9/wild type (WT) gastro-intestinal stromal tumours (GIST) who were not suitable for surgery using a risk-stratification and sequential dose escalation strategy of imatinib followed by nilotinib, in comparison with historical controls.

An analysis of the results determined the relationship between imatinib trough concentration with early metabolic response in patients with GIST. The pharmacokinetics parameters were similar to those reported with clearance highly variable, suggesting the need for individualised therapy. Early metabolic response did not correlate with imatinib trough concentrations, it was hypothesised that early response assessed by PET may correlate with imatinib concentrations within the tumour.

ICECREAM – clinical trial – Cetuximab antibody treatment for colorectal cancer with a G13D gene mutation

Cetuximab is an antibody from a biological source used to treat bowel cancers. It appears not to work for tumours with some gene mutations, however several small studies had suggested that it was possible that cetuximab was effective in tumours with one particular mutation (the rare KRAS G13D mutation).

Contrary to some earlier reports, cetuximab was shown to not be a useful treatment for tumours with G13D mutations. Although the combination treatment did show a minor benefit, given the side-effects observed and uncertainty about the need for cetuximab, these results do not justify the routine use of this drug combination for patients with this type of mutation.

The outcomes were published in the Journal of Clinical Oncology in 2016.

GAP – clinical trial – Phase 2 gemcitabine and nab-paclitaxel for resectable pancreas cancer

Standard treatment for people with pancreas cancer is surgery to remove the tumour and then chemotherapy, radiotherapy, or both. Unfortunately, many patients are not fit enough to have chemotherapy after the operation. Also, for some, the chemotherapy does not have a beneficial effect.

GAP was a trial using a combination of drugs before surgery and to identify those patients who will also benefit from chemotherapy after surgery. The results were presented at the meeting of the American Society of Clinical Oncology in 2016 showing that this combination of chemotherapy administered prior to surgery is a worthwhile treatment for this patient population.

ATTAX3 – clinical trial – Panitumumab added to chemotherapy in oesophagogastric cancer

The ATTAX3 trial helped researchers by providing evidence on the value of a new combination of drugs for treating cancer of the upper digestive tract.

ATTAX3 was a phase 2 trial exploring whether a new combination of drugs would be effective in shrinking this type of tumour, while being safe. A promising antibody treatment, (panitumumab) was added to a standard chemotherapy, however it was concluded that this regimen does not substantially benefit people with oesophageal and gastric cancers. An exception to this would be if future research shows that some individuals with specific genetically selected tumours can be helped by panitumumab.

The results were published in the British Journal of Cancer in 2016.

Oesophageal Meta-analysis - Setting the standard of care for treating people with oesophageal cancer

The study, published in Lancet Oncology, showed for the first time that there is a better chance of survival if patients have chemotherapy and radiation therapy given together just before surgery, rather than surgery alone.

The study analysed data from many clinical trials. It showed conclusively that there is a 14% improvement in survival if patients receive concurrent chemotherapy and radiation therapy before surgery. This helps prevent the spread of cancerous tumours in their oesophagus, compared to surgery alone.

In March 2008, Lancet Oncology announced that this review was the fourth most read article for 2007. This demonstrates the potential for AGITG to impact on clinical care for cancer patients throughout the world.

CO.17 - clinical trial - A new targeted treatment for advanced bowel cancer

The AGITG contributed significantly to a large international clinical trial that for the first time showed that a targeted treatment approach, not involving chemotherapy, prolongs the survival of people with advanced bowel cancer.

The CO.17 clinical trial tested the drug Cetuximab in people with advanced bowel cancer. Cetuximab works by blocking receptors on the surface of the cancer cells, which in turn blocks the cancer’s ability to grow. This treatment prolonged the lives of people on the trial by a few months. Results from this study were published in the New England Journal of Medicine in 2007.

Furthermore, additional research within the CO.17 study into the role of the biomarker KRAS showed that a tumour’s KRAS status can predict a patient’s response to treatment with cetuximab. In particular, patients with very advanced colorectal cancer treated with cetuximab whose tumours expressed wildtype KRAS survive twice as long as patients with tumours bearing a mutated KRAS gene. These findings were published in the New England Journal of Medicine in 2008.

A follow on study was developed by NCIC in collaboration with the AGITG. CO20 tested a promising new drug, brivanib, added to cetuximab for advanced colorectal cancer. Although the treatment had some positive effects on the tumour, the treatment did not improve overall survival. The results were published in the Journal of Clinical Oncology in 2013.

TROG/AGITG 01.04 clinical trial - A treatment program for rectal cancer

The AGITG has collaborated with the Trans-Tasman Radiation Oncology Group (TROG) in undertaking a major clinical trial of 326 patients with locally advanced cancer of the rectum. The trial compared the relapse rates of patients treated with preoperative treatment programs, either one week of radiotherapy or five and a half weeks of chemoradiotherapy. Both programs have been accepted as standard-of-care in different parts of the world.

Early results comparing side-effects were presented at the 2007 European CanCer Organisation (ECCO) meeting and the results of comparing patients’ quality of life were presented at the 2008 meeting of the American Society of Clinical Oncology (ASCO). The results were published in JAMA in 2015.

MAX clinical trial - First international AGITG-led trial

The MAX clinical trial was an AGITG-led clinical trial that tested oral chemotherapy in combination with bevacizumab for advanced bowel cancer. This trial was the first for AGITG to recruit patients internationally.

The final results were published in the Journal of Clinical Oncology in 2010, and showed that adding bevacizumab to chemotherapy treatment improved progression-free survival without additional toxicity or reduction in quality of life.

Advanced GIST clinical trial - Setting the treatment standard for people with GIST in Australia

AGITG successfully brought a targeted therapy to Australia to treat patients with advanced Gastro-Intestinal Stromal Tumours (GIST).

Through the Advanced GIST clinical trial, the AGITG treated patients with the new drug therapy years before it was generally available or listed on the Australian Pharmaceutical Benefits Scheme (PBS). IMATINIB (Gleevec) leads to a five-fold increase in survival. It acts on GIST by blocking growth signals in tumour cells that are continuously activated as a result of genetic mutations.

INTEGRATE clinical trial - A new biological treatment for oesophageal cancers

INTEGRATE was the first study to show that regorafenib, which inhibits the growth of blood vessels, is active against oesophageal cancer and is safe. These results were published in the Journal of Clinical Oncology in 2016.

The trial had patients enrolled in Australia, New Zealand, South Korea and Canada. Regorafenib improved progression-free survival. This benefit was greater in the group of participants from South Korea, which could be due to genetic or molecular differences. A follow-on study was developed following the success of INTEGRATE, a phase III trial (INTEGRATE II), to
explore survival and the reasons for regional differences.

SCOT clinical trial - Reducing the toxic effects of chemotherapy by shortening the treatment dose and time

The standard adjuvant chemotherapy treatment for colorectal cancer is combination chemotherapy including oxaliplatin for 6 months. Oxaliplatin is a nerve toxin and damage to the nerves is cumulative, related to the dose level, and potentially irreversible.

The SCOT trial randomised patients to 3 months or 6 months of treatment. In general, the rate of relapse was similar in both groups, but those on the shorter regimen had less toxicity. The results were presented at the meeting of the American Society of Clinical Oncology in 2017. Individual risk factors and benefits are still being studied.