PrimeRT

Priming the Tumour MicroEnvironment for Effective Treatment with Immunotherapy in Locally Advanced Rectal Cancer. A Phase II trial of Durvulamab (MEDI 4736) in Combination with Extended Neoadjuvant Regimens in Rectal Cancer

Trial summary:

In rectal cancer, strategies to enhance local treatment responses by expanding neoadjuvant regimens are sought to enable organ preservation in more patients. The addition of systemic FOLFOX post-chemoradiotherapy and post short course radiotherapy has been reported with encouraging results demonstrating higher rates of complete response than with radiotherapy based treatment alone. Immunotherapy using PD-1/ PD-L1 inhibition is recognised to be effective in mismatch repair deficient colorectal cancer (dMMR)… At baseline few rectal tumours (10-20%) demonstrate moderate-high grade CD3+ responses within the tumour microenvironment but there is evidence radiotherapy (e.g. SCRT or CRT) and systemic chemotherapy (FOLFOX) induce favourable immune responses. We plan a phase II trial to evaluate the potential treatment efficacy of anti-PD-L1, Durvalumab in addition to either SCRT or CRT with FOLFOX in the gap to post treatment assessment.

This trial will evaluate rates of complete response in each arm as it’s primary endpoint in addition to safety and toxicity as secondary endpoints. It is a translationally rich trial which involves the collection of biospecimens prior to, during and following treatment in order to understand the molecular and immunological factors underpinning treatment response.

This is a phase II, 1:1 randomised trial with a safety lead-in.

RT QA summary:

All QA activity will be streamlined with previous trial QA, where applicable. Please contact the RTTQA Group directly using the contact details below to discuss.

QA Process	QA Activity	Required for Trial	Additional Details
Pre-Accrual	Facility Questionnaire
	Outlining Benchmark Case
	Planning Benchmark Case
	Dummy Run
During Accrual	Individual Case Review		Of at least the first patient case
	Data collection		Anonymised: PAF, brief clinical history, diagnostic imaging reports, planning CT, structures, plan and plan dose cube
Dosimetry
QA Streamlining			All other current lower GI trials considered, discuss with the RTTQA contact

RTTQA contact: PrimeRT.RTTQA@wales.nhs.uk

Chief investigator: Mr Campbell Roxburgh, Consultant Colorectal Surgeon

RT Lead: Professor Richard Adams, Consultant Clinical Oncologist

Trials Unit: Cancer Research UK Clinical Trials Unit, The Beatson West of Scotland Cancer Centre; liz-anne.lewsley@glasgow.ac.uk

Sponsor: NHS Greater Glasgow and Clyde/University of Glasgow (GN18ON303)

Funder: AstraZeneca