PURPOSE The AKT pathway is upregulated in cervical cancer. This trial aimed to investigate whether the protease AKT pathway inhibitor (nelfinavir mesylate), in addition to chemoradiation (CRT) and image-guided brachytherapy (IGBT), could improve disease-free survival (DFS). METHODS NELCER (ClinicalTrials.gov identifier: NCT03256916 ), a phase III adaptive trial, randomly assigned patients with stage III cervical cancer (International Federation of Gynecology and Obstetrics 2018) to CRT and IGBT (standard arm) or in combination with nelfinavir (test arm). Patients in the test arm received nelfinavir 1,250 mg twice a day starting 7-10 days before and during CRT. The primary end point was 3-year DFS. Secondary end points included locoregional control, overall survival, adverse events, and quality of life. Disease-specific survival (DSS) was also estimated. The study planned to randomly assign 348 patients to detect a hazard ratio (HR) of 0.66. Futility analysis was scheduled at 32 events. RESULTS Ninety-two patients were recruited at the time of futility analysis. The stage was IIIA-B (43.5%), IIIC1 (48.9%), and IIIC2 (7.6%) patients. The median prescribed dose to high-risk clinical target volume was 88 Gy 10 (IQR, 83.6-92 Gy 10 ). At a median follow-up of 34.9 months (29-40.8), the 3-year DFS was 71% (95% CI, 0.58 to 0.86) in the standard arm and 56% in the nelfinavir arm (95% CI, 0.43 to 0.70; HR, 1.34 0.66 to 2.7; P = .40). The nelfinavir arm had a higher incidence of acute grade ≥ 3 (8.7% v 0%, P = .04) GI effects. The 3-year DSS was 82% (95% CI, 0.70 to 0.95) in the standard arm and 57% (95% CI, 0.43 to 0.75) in the nelfinavir arm (HR of 1.97 0.87 to 4.4, P = .09). The z-value was 0.74. CONCLUSION The 3-year DFS did not cross prespecified statistical boundary; however, on the basis of DSS and acute adverse events, nelfinavir was not considered clinically efficacious, and the trial was stopped at the first interim analysis.
Chopra et al. (2026) studied this question.