A phase 1 safety and feasibility trial of a ketogenic diet plus standard of care for patients with recently diagnosed glioblastoma.

Despite great interest, there is limited clinical evidence to support the use of a ketogenic diet (KD) for cancer patients. We conducted a single-arm phase 1 trial of a KD among patients with recently diagnosed glioblastoma (GBM) receiving standard-of-care (SOC) treatment. Adults with GBM within 3 months of diagnosis followed a supervised 16-week intervention of a 3:1 KD (Fat(g): Carbohydrate + Protein(g)) plus SOC chemoradiation. The primary outcome was safety, evaluated by weekly assessments of weight and body mass index (BMI). Secondary outcomes included feasibility (pre-specified as > 50% of patients maintaining blood ketone levels > 0.3 mM over 50% of study days), progression-free survival (PFS), overall survival (OS), health-related quality-of-life, and cognitive function. Twice daily blood glucose and ketones, weight/BMI, physical activity, and sleep were assessed by remote monitoring. Seventeen patients were evaluable: 53% women, median age 55, median Karnofsky Performance Status 85. All subjects met the primary safety objective with no instances of excessive weight loss or related serious adverse events. Adherence was high: all 17 patients maintained nutritional ketosis (≥ 0.3 mM/dL) > 50% of study days. Median PFS and OS were 12.9 months and 29.4 months from KD initiation respectively. Quality of Life, symptom control, and cognitive function remained stable or improved, although these did not reach statistical significance. This phase 1 trial demonstrates that KD is safe and feasible for GBM patients receiving SOC, may improve outcomes, and provides a foundation for an NCI-funded multicenter randomized diet trial to assess efficacy that is currently underway.