Small Cell CarcinomaPhase 1/2NCT07206563
Penfluridol for Relapsed/Refractory Small Cell Cancers
A Phase 1/2 study testing Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer in people with Small Cell Carcinoma and Small Cell Carcinoma of Lung, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Small Cell Carcinoma, Small Cell Carcinoma of Lung, Small Cell Lung Cancer ( SCLC )
- What is being tested?
- Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2025to 1 Oct 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- Expected survival of ≥12 weeks.
- Recovery of prior anticancer treatment toxicities to ≤Grade 1 (except for alopecia, pigmentation, or other toxicities deemed non-safety risks by the investigator); for irreversible toxicities that are not expected to worsen with study drug administration (e.g., hearing loss), inclusion may be considered after consultation with the medical monitor. Recovery of peripheral neuropathy to ≤Grade 2 after prior use of cisplatin or etoposide may be considered for inclusion after consultation with the medical monitor. For late toxicities caused by radiotherapy that cannot be recovered, inclusion may be considered after consultation with the medical monitor.
- 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.
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430030
Bai Hu, MD., +8615791797686, baihu_tjh@163.com
baihu_tjh@163.com
About this study
Official title: Penfluridol for Relapsed/Refractory Small Cell Lung Carcinoma and Small Cell Cervical Cancer: An Open-Label, Multicenter, Single-Arm Ib/II Trial
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.
Read the detailed description
Rationale and Preclinical Justification Small-cell carcinoma of the lung (SCLC) and cervix (SCCC) represent aggressive malignancies with a paucity of effective therapeutic options upon relapse, leading to dismal survival outcomes. To address this unmet need, a high-throughput drug screening was conducted utilizing patient-derived organoid (PDO) models of SCLC and SCCC. This screening identified penfluridol, a first-generation antipsychotic drug with a long-established human safety profile, as a potent inhibitor of small-cell carcinoma growth. Its anti-tumor efficacy is mechanistically attributed to dual pathways: 1) antagonism of dopamine receptor D2 (DRD2), a target implicated in cancer stem cell maintenance and proliferation, and 2) induction of metabolic stress via inhibition of glycolysis, leading to AMPK/FOXO3a-mediated apoptosis. Notably, penfluridol's inherent ability to penetrate the blood-brain-barrier positions it as a potential therapeutic candidate for addressing the common site of metastasis in SCLC. This study aims to clinically reposition penfluridol based on this compelling preclinical evidence.
Study Design and Technical Considerations This is an open-label, multicenter, seamless Phase Ib/II trial. The design integrates a dose-finding phase followed by an efficacy expansion phase to efficiently evaluate both safety and preliminary activity.
Phase Ib (Dose Escalation): Utilizes a standard 3+3 design to determine the Recommended Phase II Dose (RP2D). The starting dose is 20 mg orally once weekly, with planned escalation to 40 mg and 60 mg. The RP2D will be defined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during the first 21-day cycle. Pharmacokinetic profiling will be performed to characterize exposure at each dose level.
Phase II (Expansion Cohort): Aims to estimate the objective response rate (ORR) at the RP2D. The study employs a Simon's two-stage minimax design to test the null hypothesis that the true ORR is ≤10% against an alternative of ≥30%, with 90% power and a one-sided alpha of 0.05. This design allows for early termination for futility.
Biomarker Strategy: The protocol incorporates a comprehensive exploratory biomarker plan. This includes correlative analyses of DRD2 expression in archival tumor tissue, serial monitoring of cell-free DNA (cfDNA) for dynamic changes in tumor burden, and assessment of metabolic response via FDG-PET imaging to elucidate potential biomarkers of response and resistance.
Safety Monitoring Focus Given penfluridol's known safety profile from psychiatric use, the protocol institutes enhanced, protocol-specified monitoring for specific risks. This includes regular assessments for extrapyramidal symptoms (using the RSESE scale) and rigorous cardiac monitoring (serial ECGs for QTc interval assessment) beyond standard CTCAE reporting. An independent Data Monitoring Committee (IDMC) will review accumulating safety and efficacy data.
- Conditions
- Small Cell Carcinoma, Small Cell Carcinoma of Lung, Small Cell Lung Cancer ( SCLC ), Small Cell Cervical Carcinoma
- Being tested
- Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer
- Keywords
- Small cell cervical carcinoma, small cell lung carcinoma, Relapsed/refractory, Phase Ib/II, DRD2 targeting
- Medical subject headings
- Carcinoma, Small Cell, Small Cell Lung Carcinoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical CancerDrug
Also called Semap, R-16341
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
To evaluate the safety and tolerability profile of oral penfluridol.
Measured: From the first dose of study drug until 30 days after the last dose, assessed up to approximately 24 months.
Duration of Response (DOR)
To assess the durability of tumor responses.
Measured: From the first documented objective response until disease progression or death (whichever occurs first), assessed up to approximately 24 months.
Progression-Free Survival (PFS)
To assess disease control.
Measured: From the first dose until disease progression or death (whichever occurs first), assessed up to approximately 24 months.
Overall Survival (OS)
To evaluate the overall survival benefit.
Measured: From the first dose until death from any cause, assessed up to approximately 36 months.
Disease Control Rate (DCR)
To evaluate the proportion of patients achieving disease control.
Measured: From the first dose until documented disease progression, assessed up to approximately 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2025
- Study start1 Oct 2025 (estimated)
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 33 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peng Wu, PhD, Principal investigator, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07206563
- Sponsor's protocol ID
- UHCT250646
- Status last verified
- Sep 2025
- First submitted
- 16 Sep 2025
- Last updated
- 3 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Penfluridol for Relapsed/Refractory Small Cell Lung Carcinoma and Small Cell Cervical Cancer: An Open-Label, Multicenter, Single-Arm Ib/II Trial
- ClinicalTrials.gov ID
- NCT07206563
- Acronym / sponsor ID
- UHCT250646
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 33 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 3 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Rationale and Preclinical Justification Small-cell carcinoma of the lung (SCLC) and cervix (SCCC) represent aggressive malignancies with a paucity of effective therapeutic options upon relapse, leading to dismal survival outcomes. To address this unmet need, a high-throughput drug screening was conducted utilizing patient-derived organoid (PDO) models of SCLC and SCCC. This screening identified penfluridol, a first-generation antipsychotic drug with a long-established human safety profile, as a potent inhibitor of small-cell carcinoma growth. Its anti-tumor efficacy is mechanistically attributed to dual pathways: 1) antagonism of dopamine receptor D2 (DRD2), a target implicated in cancer stem cell maintenance and proliferation, and 2) induction of metabolic stress via inhibition of glycolysis, leading to AMPK/FOXO3a-mediated apoptosis. Notably, penfluridol's inherent ability to penetrate the blood-brain-barrier positions it as a potential therapeutic candidate for addressing the common site of metastasis in SCLC. This study aims to clinically reposition penfluridol based on this compelling preclinical evidence.
Study Design and Technical Considerations This is an open-label, multicenter, seamless Phase Ib/II trial. The design integrates a dose-finding phase followed by an efficacy expansion phase to efficiently evaluate both safety and preliminary activity.
Phase Ib (Dose Escalation): Utilizes a standard 3+3 design to determine the Recommended Phase II Dose (RP2D). The starting dose is 20 mg orally once weekly, with planned escalation to 40 mg and 60 mg. The RP2D will be defined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity (DLT) during the first 21-day cycle. Pharmacokinetic profiling will be performed to characterize exposure at each dose level.
Phase II (Expansion Cohort): Aims to estimate the objective response rate (ORR) at the RP2D. The study employs a Simon's two-stage minimax design to test the null hypothesis that the true ORR is ≤10% against an alternative of ≥30%, with 90% power and a one-sided alpha of 0.05. This design allows for early termination for futility.
Biomarker Strategy: The protocol incorporates a comprehensive exploratory biomarker plan. This includes correlative analyses of DRD2 expression in archival tumor tissue, serial monitoring of cell-free DNA (cfDNA) for dynamic changes in tumor burden, and assessment of metabolic response via FDG-PET imaging to elucidate potential biomarkers of response and resistance.
Safety Monitoring Focus Given penfluridol's known safety profile from psychiatric use, the protocol institutes enhanced, protocol-specified monitoring for specific risks. This includes regular assessments for extrapyramidal symptoms (using the RSESE scale) and rigorous cardiac monitoring (serial ECGs for QTc interval assessment) beyond standard CTCAE reporting. An independent Data Monitoring Committee (IDMC) will review accumulating safety and efficacy data.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer | Experimental | Drug: Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical CancerIntervention: 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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).
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical CancerAlso: Semap, R-16341Intervention: 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 |
Primary outcome
Recommended Phase II Dose (RP2D) of penfluridol [Phase Ib]
Time frame: 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).
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.
Objective Response Rate (ORR) [Phase II]
Time frame: 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.
To evaluate the antitumor activity of oral penfluridol at the RP2D as measured by the Objective Response Rate.
5 secondary outcomes
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Time frame: From the first dose of study drug until 30 days after the last dose, assessed up to approximately 24 months.
Duration of Response (DOR)
Time frame: From the first documented objective response until disease progression or death (whichever occurs first), assessed up to approximately 24 months.
Progression-Free Survival (PFS)
Time frame: From the first dose until disease progression or death (whichever occurs first), assessed up to approximately 24 months.
Overall Survival (OS)
Time frame: From the first dose until death from any cause, assessed up to approximately 36 months.
Disease Control Rate (DCR)
Time frame: From the first dose until documented disease progression, assessed up to approximately 24 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2025.
- Individual participant dataSharing planned: No
Related trials for Small Cell Carcinoma
Active, not recruitingPhase 3
A Study to Compare the Efficacy, Safety, Pharmacokinetics, and Immunogenicity Between SB27 and Keytruda in Subjects With Metastatic Non-squamous Non-small Cell Lung Cancer
Non-small Cell Lung Cancer Stage IV
RecruitingPhase 3
A Study of Calderasib (MK-1084) Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004/KANDLELIT-004)
Non-small Cell Lung Cancer
Active, not recruitingPhase 3
Testing the Timing of Pembrolizumab Alone or With Chemotherapy as First Line Treatment and Maintenance in Non-small Cell Lung Cancer
Lung Non-Squamous Non-Small Cell Carcinoma, Stage IIIB Lung Cancer AJCC v8
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK112 in Patients With Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer
RecruitingPhase 2
A UGT1A1 Genotype-Directed Study of Belinostat Pharmacokinetics and Toxicity
Carcinoma, Neuroendocrine, Tumor, Neuroendocrine
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peng Wu, PhD principal investigator
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Penfluridol Monotherapy for Relapsed/Refractory Small-Cell Lung or Cervical Cancer in people with Small Cell Carcinoma and Small Cell Carcinoma of Lung, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 3 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Peng Wu, PhD (+8613995573729, pengwu8626@tjh.tjmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended Phase II Dose (RP2D) of penfluridol [Phase Ib] (time frame: 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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2025.