CRAIN Trial Explores a New Treatment Approach for Cervical Cancer

The Southampton Clinical Trials Unit (SCTU) – a Cancer Research UK core‑funded and NIHR‑supported unit – has played a central role in delivering the CRAIN trial, an early‑phase clinical study testing a promising new treatment option for cervical cancer.

Working closely with University Hospital Southampton , SCTU specialises in the design, delivery, and analysis of major multi ‑ centre studies, acting as a leading hub for early ‑ phase and translational cancer research.

A trial aiming to improve treatment options

While chemoradiotherapy remains an effective standard treatment for cervical cancer, it can cause significant long ‑ term side effects – and around half of patients will experience a return of their cancer. This creates an urgent need for therapies that can improve survival while reducing treatment burden.

The CRAIN trial , now successfully completed, set out to explore one such option. Delivered by SCTU and led nationally by Professor Peter Hoskin (University of Manchester and The Christie NHS Foundation Trust), the study has now finished data collection, with results undergoing final analysis ahead of publication later this year.

Targeting apoptosis: a new direction in treatment

One promising avenue for improving outcomes is targeting apoptosis, the body’s natural process of removing damaged or ageing cells. Many cancers evade this mechanism, which allows tumour cells to survive and multiply.

Tolinapant, the drug tested in CRAIN, is an Inhibitor of Apoptosis Proteins (IAP). Its purpose is to switch apoptosis back on within cancer cells.

Laboratory studies have shown that adding tolinapant to standard chemoradiotherapy increases the number of cancer cells destroyed.

“The key outcome of CRAIN was to investigate escalating doses of tolinapant alongside chemoradiotherapy to determine the maximum tolerated dose and identify a safe, recommended dose for future Phase II studies, and we have achieved that,” explains Marina Lee, Trial Manager at Southampton Clinical Trials Unit.

With the clinical phase complete, experts at the Manchester Cancer Research Centre, are now analysing the biological samples collected during the study. Their work will help determine:

• How tolinapant behaves inside the body
• How it interacts with both radiotherapy and chemotherapy
• Which biological markers could predict treatment response

These insights may ultimately help identify which patients are most likely to benefit from adding tolinapant to their treatment programme.

What comes next?

The findings from CRAIN will inform whether a larger Phase II trial should proceed. This next step would examine whether combining tolinapant with standard chemoradiotherapy can:

• destroy more cancer cells
• reduce the likelihood of recurrence
• lessen long ‑ term side effects
• improve overall survival

The hope is ultimately to bring safer, more effective treatment options to patients living with cervical cancer.