A phase 2a trial has revealed encouraging early evidence for a potential new strategy to prevent cancer metastasis in patients with high-risk solid tumours, after investigators reported fewer metastatic recurrences and no metastasis-related deaths among treated participants.
The study, conducted by Cumberland Pharmaceuticals and Vanderbilt Health, evaluated an investigational therapy in patients with solid tumours considered at high risk of early metastatic recurrence, including breast, lung, pancreatic, soft tissue, bladder and renal cancers.
Safety endpoint achieved
The randomised, double-blind, placebo-controlled trial met its primary endpoint, demonstrating that the treatment was safe and well tolerated in this patient population.
Rates of treatment-related adverse events were similar between the placebo and active treatment groups, while no serious adverse events linked to study treatment were identified. Investigators also reported no statistically significant difference in treatment discontinuation rates between the two arms.
A total of 29 participants were enrolled in the study, with 19 receiving the investigational therapy and 10 receiving placebo. Patients were treated for 12 months following completion of all cancer-related therapies and surgical procedures, before entering a further 12-month follow-up period.
Encouraging efficacy signals
Although the study was designed primarily to assess safety and was not powered to demonstrate efficacy, investigators observed favourable trends across several measures linked to metastatic disease.
At 12 months, 50% of participants in the placebo arm experienced distant metastatic recurrence, compared with 17% of those receiving the investigational therapy (p=0.091).
Notably, three deaths due to distant metastatic disease occurred in the placebo group, while no metastasis-related deaths were reported among treated participants (p=0.037).
Dr Ben Ho Park, Vanderbilt-Ingram Cancer Center, said: “A therapeutic intervention aimed at metastasis prevention for cancer patients with high risk of recurrence that is given during the period of ‘watchful waiting’ could be groundbreaking if proven beneficial in larger scale investigations.
“We look forward to pursuing those pivotal studies as we relentlessly look for treatments to benefit patients living with cancer.”
Targeting the metastatic process
While many oncology therapies act directly on tumour cells, few treatments specifically target the biological mechanisms that enable cancer to spread.
The investigational approach focuses on blocking thromboxane A2 receptor signalling, with the aim of reducing platelet activation and limiting tumour cells’ ability to migrate, invade distant organs and evade immune surveillance.
Supporting evidence for the programme includes genetic analyses linking thromboxane receptor variants with increased metastatic risk, alongside preclinical studies demonstrating reduced metastasis across several animal models.
A.J. Kazimi, CEO, Cumberland Pharmaceuticals, said: “The favourable safety profile of ifetroban in this patient population, combined with the efficacy signals observed in this study, supports continued investigation of ifetroban as a candidate for metastasis prevention.
“The contributions of the Vanderbilt Health team have been essential to advancing this programme.”
Next steps
The phase 2a findings will now inform future studies designed to confirm efficacy and further characterise the therapy’s safety profile.
If replicated in larger trials, the approach could offer a new treatment option during the post-treatment surveillance period, when patients remain vulnerable to microscopic metastatic disease despite being in clinical remission.
Featured image: Mikel Taboada on Adobe Stock
