Penfluridol for Relapsed/Refractory Small-Cell Carcinoma of the Lung or Cervix: A Multicenter, Open-Label, Single-Arm Phase Ib/II Trial This study evaluates the safety and anti-tumor activity of oral penfluridol, a first-generation antipsychotic that pre-clinically inhibits small-cell carcinoma (SCC) growth via DRD2 blockade, metabolic reprogramming and apoptosis induction. After ≥2 prior systemic regimens, 33 adult patients (18-75 y) with measurable, metastatic or recurrent lung or cervical SCC will be enrolled across five Chinese centers. A 3+3 dose-escalation (Ib) will establish the recommended Phase II dose (RP2D); an expansion cohort (II) will examine objective response rate (ORR, RECIST 1.1). Secondary end-points include duration of response, progression-free survival, overall survival, safety and exploratory biomarkers. Key inclusion: ECOG 0-1, adequate organ function, no active brain metastases. Penfluridol is administered once weekly, dose-escalated from 20 mg to RP2D, continued until progression or intolerance. Patients receive free study drug, PET imaging and laboratory monitoring.
Patients aged 18 to 75 years, inclusive, regardless of gender.
Histologically or cytologically confirmed small-cell carcinoma of the lung or cervix that is not curable by surgery or radiochemotherapy.
Have received at least two prior systemic treatment regimens, including etoposide and platinum-based chemotherapy, and have experienced disease progression.
No receipt of investigational or approved cytotoxic chemotherapy within 28 days before enrollment; no receipt of alkylating agents within 42 days before enrollment; no receipt of investigational or approved targeted therapy within 28 days or 5 half-lives before enrollment (whichever is shorter, but not less than 14 days); no radiotherapy within 14 days before enrollment.
Histological diagnosis of squamous cell carcinoma, adenocarcinoma, or other non-small-cell types of lung or cervical cancer.
Concurrent enrollment in another clinical trial, unless it is an observational, non-interventional study or the follow-up period of an interventional study.
Known hypersensitivity to any component of penfluridol or similar compounds with comparable chemical or biological properties.
Prior exposure to penfluridol.
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Lead sponsor