AGITG Joint Working Party Meeting 10 May 2019

AGITG Joint Working Party Meeting 10 May 2019

May 22, 2019

Lower GI Working Party

Trial Updates

  • SPAR recruitment is underway with New Zealand sites confirmed for activation.
  • ASCOLT sample size has increased from 1200 to 1587.
  • A Cancer Australia grant for additional funding has been submitted.
  • DYNAMIC-III and DYNAMIC-Rectal are both recruiting well.  In regard to tissue availability, sites with both DYNAMIC-Rectal and SPAR open should give precedence to DYNAMIC-Rectal.
  • RENO has officially opened at one site and has commenced recruitment.
  • The protocol for MONARCC is being amended to modify the inclusion criteria to include all patients over the age of 70 years, with the aim of increasing recruitment.
  • LIBERATE is recruiting quickly (82/100).
  • MODULATE has recruited and reached its interim analysis quickly. Recruitment is currently paused at 53 participants, awaiting the outcome of the first safety analysis.
  • OXTOX is currently undergoing the HREC review, with recruitment expected to begin in the second half of 2019.

Concept Updates

RoLaCaRT: A PHASE III INTERNATIONAL MULTICENTRE COMPARISON OF PATIENT-ORIENTED CLINICAL OUTCOMES FOR PATIENTS UNDERGOING RIGHT HEMICOLECTOMIES PERFORMED EITHER ROBOTICALLY OR LAPAROSCOPICALLY FOR MALIGNANCIES OF THE COLON: ROBOTIC BOWEL TRIAL.

RoLaCaRT was presented at the last Joint Working Party meeting in December 2018. The trial was formerly known as ROBOT. It is designed to investigate whether robotics will provide greater advantages, improved rates of successful surgery and better patient-oriented outcomes. The trial is expecting a recruitment period of two years with 20 sites in Australia with the potential for international sites to come on board down the track. It is likely that 40 surgeons will be accredited. An NHMRC grant application has just been submitted. The trial will be an important step in determining future practices.

ReLaPSeD: RELOOK LAPAROSCOPY FOR PERITONEAL SURFACE DISEASE TRIAL.

ReLaPSeD is a study of the role of re-look in laparoscopy in patients with high-risk colorectal cancer (T4 cancers and perforated cancers), where there is a high risk of peritoneal recurrence. It was submitted for pilot and seed funding in 2018 but was not successful. ReLaPSeD has commenced a pilot phase study of 8 patients at the Royal Prince Alfred Hospital, despite no funding. The first laparoscopy is expected to take place in a few weeks. Peter Mac is the 2nd site awaiting ethics approval for this study.

New Concepts

ADJ ICI AFTER CRT FOR MUC SQU CANCERS IMMUNOTHERAPY: A GLOBAL, BASKET, RANDOMISED PHASE III INTERGROUP TRIAL OF ADJUVANT IMMUNOTHERAPY AFTER DEFINITIVE CHEMORADIATION FOR MUCOSAL SQUAMOUS CELL CARCINOMAS OF THE ANUS, HEAD AND NECK, CERVIX, VAGINA, VULVA AND PENIS.

This basket trial for rare cancers takes a global perspective. At the meeting, it generated a lot of interest but it was noted that it may face low recruitment issues due to the nature of rare cancer trials. It is to be led from the UK with opportunity for contribution from Australia and New Zealand. There was general support and interest for the trial. The study includes collaboration with other Collaborative Trial Groups including ANZGOG.

ASPIRIN: A PHASE II STUDY OF REGORAFENIB COMBINED WITH ASPIRIN IN RAS MUTATED ADVANCED COLORECTAL CANCER.

The proposed clinical trial is a randomised, non-comparative, multi-centre, prospective phase II study with a safety run-in, to determine the preliminary activity and safety of high dose aspirin with regorafenib in RAS mutated metastatic colorectal cancer patients who have failed standard of care therapy. The concept was submitted to the 2018 AGITG New Concepts Symposium. Queries over toxicity and the duration of SAEs were raised. A phase I study was suggested to investigate both tolerance and whether patients could be treated with a lower dose of regorafenib.

Upper GI Working Party

Trial Updates

  • The current TOPGEAR grant has been extended.
  • Representatives from Australia, Japan and Bayer are proposing that INTEGRATE II be re-designed into INTEGRATE III including immunotherapy.
  • Recruitment for NABNEC is continuing slowly, as it is a rare cancer trial. It was noted that as patients give consent to use tissue for translational work, clinicians are requested to advise when patients have an operation or biopsy, so that the specimen can be accessed by the laboratory.
  • CONTROL NETs is currently in follow up as accrual was completed in 2018. Data is undergoing assessment with an aim of presenting at ASCO GI in 2020.
  • ACTICCA-1 is starting to attract worldwide attention, with particular interest from Canada.
  • The gem-Abraxane arm of DYNAMIC-Pancreas may need to close as a result of the APACT study findings recently released by Celgene, however this is yet to be determined by the Trial Management Committee
  • MASTERPLAN National Guidelines on giving pancreas SBRT have been written. A translational research committee is now in place. The study is expected to open in two months.
  • ALT-GIST will be presented at the poster presentation and discussion at ASCO.

Concept Updates

BALLAD: A TRIAL TO EVALUATE THE POTENTIAL BENEFIT OF ADJUVANT CHEMOTHERAPY FOR SMALL BOWEL ADENOCARCINOMA.

This rare cancer trial will not be supported by AGITG as it reflects common practice in Australia. In the future the AGITG will encourage setting up a working group to develop a model similar to the ‘Just in Time’ model in the UK. This would be a timely and cost-effective method, minimising inventory and increasing efficiency, however requires considerable changes to the current regulatory framework in Australia.

IGPG: PHASE I OPEN LABEL TRIAL OF INTRAPERITONEAL PACLITAXEL IN COMBINATION WITH INTRAVENOUS CISPLATIN AND ORAL CAPECITABINE IN PATIENTS WITH ADVANCED GASTRIC AND PERITONEAL CANCER.

This was a phase I open label study with 15 patients, recruited into 3 cohorts with a median age of 61-82. All had stage 4 disease and had not received previous chemotherapy. It was concluded that the procedure is safe and the recommended dose is 30mg/m2. Follow up efficacy and survival data is to be reported at ASCO. A potential study design for IPGP 2 will be submitted to the AGITG Idea Generation Workshop for further development.

New Concepts

LOWGEAR: THE PREVALENCE AND SIGNIFICANCE OF SARCOPENIA IN PATIENTS WITH OPERABLE ADENOCARCINOMA OF THE STOMACH OR GASTRO-OESOPHAGEAL JUNCTION UNDERGOING TREATMENT WITH CURATIVE INTENT AND THE IMPACT OF ALTERED BODY COMPOSITION ON CHEMOTHERAPY DELIVERY.

LOWGEAR is a substudy of TOPGEAR, looking at low muscle mass in the TOPGEAR patient population and the impact of the altered body composition on outcomes. An NHMRC grant was unsuccessful in 2018. As a result, LOWGEAR-LITE is also proposed. To be funded with local funding through St Vincent’s Hospital, the study would run at Peter MacCallum Cancer Centre and Monash Hospital for 54 patients and would assess feasibility and potential cost. LOWGEAR-LITE is value-adding and does not require the collection of any additional data points. The results could inform a large-scale AGITG-sponsored trial. There was widespread interest in LOWGEAR-LITE and it was noted that if it succeeds, there would be a lot of interest in LOWGEAR.

HIGHLANDER: PHASE II STUDY OF HIGH VERSUS STANDARD DOSE LANREOTIDE ESCALATING RESPONSE FOR ADVANCED GAPNENS

Highlander investigates whether long-acting SSAs above the standard dose improve PFS compared to standard dose SSAs. HIGHLANDER provides an opportunity to improve the use of SSAs for NET treatment. There was an overall agreement and support for HIGHLANDER. There is interest from the AGITG to sponsor the study with the Canadian Cancer Trials Group. Feedback is to be given to them for further development.

STOP-NET: A SINGLE ARM, PROSPECTIVE TRIAL OF CEASING SOMATOSTATIN ANALOGUES FOLLOWING COMPLETION OF PEPTIDE RECEPTOR RADIONUCLIDE THERAPY (PRRT) WITH LUTETIUM 177.

A single-arm feasibility study is proposed with an endpoint of establishing the rate at which SSAs are successfully withdrawn after PRRT. After follow-up, the rate of restarting SSAs will be established and QoL symptoms will be measured. The study would be conducted at the five centres in Australia that perform PRRT. The follow-up protocol needs to be formalised, as it would vary between the centres. An Innovation Fund application will be submitted for 2019.

POSITRON IMAGIN OF CELL DEATH FOR PREDICTION OF RESPONSE TO NEOADJUVANT THERAPY IN RECTAL AND OESOPHAGEAL CARCINOMA.

In order to effectively assess response to neoadjuvant therapy in carcinomas, a new technique for imaging cell death has been invented. This is a synthetic shock protein-90 alkylator called Cell Deatlh Indicater-PET CT. This is currently being assessed in a first-in-human study (oesophageal) at the Prince of Wales Hospital in Sydney. As there is currently no funding for the study, various grant opportunities are being pursued.

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