Trial Updates: August 2019

The LOWGEAR substudy is in progress

The LOWGEAR body composition study is in progress as a substudy of the TOPGEAR trial by the trial management committee.

LOWGEAR would be the first prospective study of body composition, and one of the first looking at body composition over the course of a patient’s treatment and cancer trajectory.

Traditionally, clinicians have used BMI to assess patients’ fitness for chemotherapy and ability to get through treatment.

“What we know now is that BMI and whether someone has lost weight or not is not the best way of knowing what’s going on in terms of body composition,” says Dr Melissa Moore, who is leading the study. “We’re aiming to investigate sarcopenia, or low muscle mass, and also look at muscle quality.”

LOWGEAR in the TOPGEAR patient population and the impact of altered body composition on outcomes.

Abnormal body composition is a key component of cancer cachexia and in particular low muscle mass or sarcopenia. The correlation of sarcopenia with survival outcomes could be integrated into treatment decisions and other interventions.

The study’s hypothesis is that sarcopenia impacts on the ability of patients to receive full course perioperative treatment.

The body composition of TOPGEAR patients would be assessed by the radiology department at St Vincent’s hospital, using CT scans at four different time points. Dr Moore notes that TOPGEAR study offers a unique opportunity for this kind of analysis.

“There is a wealth of information with those CT scans, and because the patients are having chemotherapy we would have height and weight information as well, plus pre-existing patient reported outcome data,” she says. “So it struck me that without adding any extra parameters, there was a whole heap of extra information we could get out of the TOPGEAR study without any increased imposition for patients.”

Discussions are currently underway for LOWGEAR to begin analysis of patient data.

More information about TOPGEAR is available here.

MODULATE reopens following interim analysis

The safety monitoring committee for the MODULATE study has reviewed the interim analysis, and both treatment arms are now set to reopen to accrual.

MODULATE aims to test whether it is possible to reverse the resistance of MSS colorectal cancer to PD1 inhibition by combining the PD1 inhibitory nivolumab with other drugs designed to stimulate lymphocyte infiltration of tumours.

The study requires an additional 37 patients to reach its recruitment target of 90 patients. MODULATE has had very swift patient recruitment – in order for all sites to have the opportunity to open for recruitment, each site will have enrolment limited to two participants at each site pending fortnightly reviews of enrolment.

More information about MODULATE is available here.

LIBERATE is now in follow-up

niall tebbutt profile

The LIBERATE study is now in follow-up, having recruited its target of 100 participants. LIBERATE is investigating the accuracy of liquid biopsies as a method of cancer screening for tumour mutation status.

The liquid biopsy method uses blood tests to determine the presence of mutations in circulating tumour DNA (ctDNA) as opposed to testing tumour tissue obtained through surgery. This trial is studying whether liquid biopsies can be used effectively to screen for a genetic mutation called the RAS mutation in patients with advanced colorectal cancer. Specialists use RAS status to help determine which treatment will be effective for the patient.

“There have been quite a lot of changes in the technology to analyse liquid biopsies,” Associate Professor Tebbutt, Principal Investigator of LIBERATE, has said. “Some have pros and cons, some are more sensitive than others, and some are more expensive than others, so we’ll be testing a few different techniques to try and determine which is the best method.”

More information about LIBERATE is available here. 

SAC approves three MRFF ICTC applications

The AGITG Scientific Advisory Committee has approved three concepts to be submitted for the Medical Research Future Fund’s International Clinical Trial Collaboration program.

  1. POLEM:

POLEM is a phase three trial sponsored by the Royal Marsden NHS Trust in the UK. It is comparing the rate of disease-free survival at three years of adjuvant Avelumab after standard chemotherapy versus chemotherapy alone in patients with stage III dMMR or POLE exonuclease domain mutant colon cancer. It will recruit 402 patients in total, with 10% to be enrolled by the AGITG.

  1. RoLaCaRT:

RoLaCaRT will compare the rates of ‘successful surgery’ for patients undergoing right hemicolectomies performed either robotically or laparoscopically for malignancies of the colon. It aims to recruit over 300 participants.

  1. BALLAD:

BALLAD is evaluating the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma. This is part of a global initiative, where data will be pooled from a number of different, individual parallel prospective studies addressing the same objectives, brought together under the framework of the International Rare Cancer Initiative. BALLAD Australia will have an enrolment target of 30 patients.

Recruitment strategy for NABNEC revised

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.

In order to make the NABNEC study as accessible as possible, protocol changes and amendments have been made to NABNEC, with inclusion criteria being adapted to maximise inclusiveness for patients with NECs. So far, 32 patients have been recruited to the study out of the target of 70.

“There are translational research projects associated with the study and some of it looks really exciting,” says Associate Professor Mustafa Khasraw, Principal Investigator of the trial. “There will be a lot of hypothesis-generating research coming out of it.”

More information about NABNEC is available here.