Penfluridol for Relapsed/Refractory Small Cell Cancers

NCT07206563 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: UHCT250646
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Small Cell Carcinoma; Small Cell Carcinoma of Lung; Small Cell Lung Cancer ( SCLC ); Small Cell Cervical Carcinoma

Keywords

Small cell cervical carcinoma; small cell lung carcinoma; Relapsed/refractory; Phase Ib/II; DRD2 targeting

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose (RP2D) of penfluridol [Phase Ib]

  To determine the Recommended Phase II Dose (RP2D) of oral penfluridol for the treatment of relapsed/refractory small cell lung cancer and small cell cervical cancer.

  From the first dose until the completion of the DLT observation period (21 days) for the first cohort of patients at each dose level (The Phase Ib dose-escalation stage is anticipated to take approximately 9 months).

• Objective Response Rate (ORR) [Phase II]

  To evaluate the antitumor activity of oral penfluridol at the RP2D as measured by the Objective Response Rate.

  From the first dose of study drug until disease progression, start of new anticancer therapy, or death from any cause (whichever occurs first), assessed up to approximately 24 months.

Secondary Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events (TEAEs)

  From the first dose of study drug until 30 days after the last dose, assessed up to approximately 24 months.

• Duration of Response (DOR)

  From the first documented objective response until disease progression or death (whichever occurs first), assessed up to approximately 24 months.

• Progression-Free Survival (PFS)

  From the first dose until disease progression or death (whichever occurs first), assessed up to approximately 24 months.

• Overall Survival (OS)

  From the first dose until death from any cause, assessed up to approximately 36 months.

• Disease Control Rate (DCR)

  From the first dose until documented disease progression, assessed up to approximately 24 months.

Study Arms (1)

Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer

EXPERIMENTAL

Intervention: Penfluridol, an oral antipsychotic drug, is used as monotherapy. It targets DRD2, inhibits glycolysis, and induces apoptosis. Dosing Schedule: Phase Ib: 3+3 dose-escalation design. Initial dose 20 mg weekly, escalating to 40 mg, then 60 mg until recommended Phase II dose (RP2D) is determined based on 21-day DLT assessment. Phase II: Expansion cohort at RP2D to further evaluate safety and estimate ORR. Duration: Treatment continues until progression, unacceptable toxicity, withdrawal, or investigator decision. Monitoring: Regular AE/SAE monitoring using NCI-CTCAE v5.0. Assessments include weekly vital signs, biweekly blood tests, and ECGs every 2 weeks. Tumor response evaluated by RECIST 1.1 criteria with imaging every 2-3 cycles. Dose Modification: Adjustments made for EPS, QTc prolongation, and proteinuria. Rationale for Single-Arm Design: Chosen due to the ultra-rare patient population and lack of established comparators. Efficient for determining RP2D and ORR.

Drug: Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer

Interventions

Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer DRUG

Intervention: Penfluridol, an oral antipsychotic drug, is used as monotherapy. It targets DRD2, inhibits glycolysis, and induces apoptosis. Dosing Schedule: Phase Ib: 3+3 dose-escalation design. Initial dose 20 mg weekly, escalating to 40 mg, then 60 mg until recommended Phase II dose (RP2D) is determined based on 21-day DLT assessment. Phase II: Expansion cohort at RP2D to further evaluate safety and estimate ORR. Duration: Treatment continues until progression, unacceptable toxicity, withdrawal, or investigator decision. Monitoring: Regular AE/SAE monitoring using NCI-CTCAE v5.0. Assessments include weekly vital signs, biweekly blood tests, and ECGs every 2 weeks. Tumor response evaluated by RECIST 1.1 criteria with imaging every 2-3 cycles. Dose Modification: Adjustments made for EPS, QTc prolongation, and proteinuria. Rationale for Single-Arm Design: Chosen due to the ultra-rare patient population and lack of established comparators. Efficient for determining RP2D and ORR.

Also known as: Semap, R-16341

Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Presence of measurable disease according to RECIST 1.1 criteria; measurable lesions are defined as lesions that can be accurately measured in at least one dimension (longest diameter ≥10 mm on CT or MRI scans, and lymph nodes with short-axis diameter ≥15 mm).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival of ≥12 weeks.
• Laboratory tests: Absolute neutrophil count ≥1.5×10⁹/L; platelets ≥75×10⁹/L; hemoglobin ≥90 g/L; serum creatinine ≤1.5 times the upper limit of normal (ULN); urine protein \<2+ or 24-hour urine protein \<1.0 g; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN (or ≤5 times ULN in the presence of liver metastasis); total bilirubin ≤1.5 times ULN; albumin ≥28 g/L; coagulation function: prothrombin time (PT) and international normalized ratio (INR) ≤1.5×ULN.
• Female subjects with negative urine or blood HCG (except for menopausal and hysterectomy cases); sexually active female subjects and their partners must agree to use effective contraception (e.g., combined hormonal contraception, intrauterine device, bilateral tubal ligation, vasectomy, abstinence) during the study and for 6 months after the last dose.
• Availability of tumor specimens (paraffin-embedded blocks or frozen tissue) from prior resection or biopsy sufficient for pharmacodynamic assays (≥3 slides for immunohistochemistry IHC) (mandatory for dose-expansion cohort patients only).
• Ability to understand the study and voluntary consent to participate in the trial by the patient or their legal representative, with signed informed consent.

You may not qualify if:

• 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.
• Known presence of leptomeningeal metastasis, spinal cord compression, leptomeningeal disease, or active brain metastases. However, patients with asymptomatic brain metastases (no neurological deficits, seizures, or other typical symptoms and signs of central nervous system metastasis; no requirement for corticosteroids) or those who have been treated and are stable on imaging for at least 4 weeks before study treatment (with no new or enlarged brain metastases) and have discontinued systemic corticosteroids and anticonvulsant medications for at least 2 weeks may be included.
• Uncontrolled comorbid conditions, including but not limited to persistent or active infections or psychiatric/social conditions that would limit compliance with study requirements.
• Positive for human immunodeficiency virus (HIV) on combination antiretroviral therapy.
• Cardiovascular history or comorbidities: Known history of arrhythmias (including atrial fibrillation, tachycardia, or bradycardia), except for benign ventricular premature beats; history of CHF, MI, or stroke within the past 3 months.
• History of seizure within the past 3 months.
• Gastrointestinal dysfunction or disease that may significantly alter the absorption of penfluridol (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known history of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant.
• Uncontrolled severe medical conditions that, in the opinion of the investigator, would affect the patient's ability to receive the study treatment, such as severe internal medicine conditions, including hepatic or renal insufficiency, severe cardiovascular disease, cerebrovascular disease, uncontrolled diabetes, or uncontrolled infections.
• Pregnant or breastfeeding women; sexually active female subjects unwilling to use contraception.
• Presence of symptomatic or unstable pleural effusion, ascites, or pericardial effusion requiring repeated drainage.
• Patients deemed unsuitable for the study by the investigator.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

MeSH Terms

Conditions

Carcinoma, Small Cell; Small Cell Lung Carcinoma; Recurrence

Interventions

Penfluridol

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Peng Wu, PhD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peng Wu, PhD

CONTACT

+8613995573729; pengwu8626@tjh.tjmu.edu.cn

Bai Hu, MD.

CONTACT

+8615791797686; baihu_tjh@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Ultra-rare population * Cervical small-cell carcinoma accounts for \<2 % of all cervical cancers, and third-/later-line SCLC represents \<5 % of lung-cancer cases. * A randomized study would require prohibitively large sample sizes and prolong accrual beyond the 3-year funding window. Absence of an established active comparator * Historical controls (retrospective cohorts) show ORR ≤ 12-18 % and median PFS ≤ 2.5 months in ≥3-line therapy. * No standard-of-care regimen is approved after ≥2 prior systemic treatments, making a placebo or active-control arm ethically questionable. Signal-seeking objective * The primary goal of this first-in-class oncology application is to define the recommended Phase II dose (RP2D) and to estimate preliminary efficacy signals (ORR), not to demonstrate superiority. * A single-arm design with an explicit Simon two-stage rule (H0: ORR ≤ 10 % vs. H1: ≥15 %) provides the most efficient path to accept or reject further development with ≤33 patients.

Study Record Dates

• First Submitted: September 16, 2025
• First Posted: October 3, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)