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This clinical trial is designed to compare and evaluate the efficacy and safety of the combination therapy of Lurbinectedin plus Paclitaxel (Combination Arm) versus Paclitaxel monotherapy (Monotherapy Arm) in patients with extensive-stage small-cell lung cancer whose disease has progressed after first-line chemotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination therapy of Lurbinectedin and Paclitaxel | Experimental | The study drugs are administered every 3 weeks until disease progression or unacceptable drug-related toxicity. Lurbinectedin is given IV at 2.2 mg/m² on Day 1, Paclitaxel IV at 80 mg/m² on Days 1 and 8, and Pegylated G-CSF on Day 2, about 24 hours after chemotherapy. |
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| Paclitaxel monotherapy | Active Comparator | The study drugs are given every 3 weeks until disease progression or unacceptable drug-related toxicity. Paclitaxel is administered IV at 80 mg/m² on Days 1 and 8, and Pegylated G-CSF is given at the investigator's discretion. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lurbinectedin | Drug | Administered IV at 2.2 mg/m² on Day 1 every 21-day cycle until disease progression or unacceptable toxicity. |
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| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) | ORR is defined as the percentage of test subjects whose confirmed response was (RECIST 1.1) at least one full response (Complete Response, CR) or partial response (Partial Response, PR) before evidence of disease progression appears. The objective response rate is summarized for groups that can be evaluated for validity. The objective response rate is presented with a 95% confidence interval on both sides (assuming a normal distribution). | End of trial(approximately 3years) |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-Free Survival (PFS) according to RECIST v1.1 | PFS is defined as the period from the date of administration of the first clinical trial drug to the progression of the disease or death for any reason. The progression-free survival period is analyzed for groups that can be evaluated for validity. | End of trial (approximately 3 years) |
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Inclusion Criteria:
Age ≥ 19 years.
Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC).
Patients who have experienced disease progression following at least one prior platinum-based systemic therapy for extensive-stage small cell lung cancer, including all of the following conditions:
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
At least one measurable target lesion according to RECIST v1.1 criteria.
Predicted life expectancy of at least 12 weeks (3 months).
Adequate hematologic, renal, metabolic, and hepatic function within 14 days prior to enrollment, defined as:
Absolute neutrophil count (ANC) ≥ 1,500/μL Platelet count ≥ 100,000/μL Hemoglobin (Hb) ≥ 9.0 g/dL Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance (cCr) ≥ 60 mL/min Total bilirubin ≤ 1.0 × ULN AST and ALT ≤ 3.0 × ULN (regardless of liver metastasis) PT and aPTT ≤ 1.5 × ULN
Willingness to provide unstained slides (minimum 5, ideally 15) from archived or freshly biopsied tissue for exploratory analyses.
Female participants of childbearing potential must have a negative pregnancy test (urine) at screening. If the urine test is positive or inconclusive, a negative serum pregnancy test is required.
Female participants of childbearing potential must agree to use effective contraception during the study.
Male participants of reproductive potential must agree to use effective contraception during the study (see appendix for acceptable methods).
Voluntary written informed consent to participate in this clinical trial.
Exclusion Criteria:
Patients who have not received prior systemic therapy for small cell lung cancer (SCLC).
Patients previously treated with Lurbinectedin or Paclitaxel.
Patients with limited-stage small cell lung cancer (LS-SCLC).
Patients with symptomatic or clinically significant brain metastases (patients with asymptomatic or stable brain metastases may be eligible; any treatment for brain metastases must have been completed at least 1 week prior to the first dose of study drug).
Concomitant use of medications that may prolong the QTc interval, potent immunosuppressive agents, or drugs that may cause interstitial lung disease (ILD) is prohibited during the treatment period. If co-administration is unavoidable, prior discussion with the coordinating center is required.
Patients with active primary immunodeficiency (e.g., HIV infection), active hepatitis B, or active hepatitis C:
Patients with active interstitial lung disease (ILD) or a history of non-infectious pneumonitis requiring steroid therapy, including immune-therapy- or chemotherapy-related ILD or Grade ≥3 pulmonary complications. (Patients with previously resolved infectious pneumonia without current clinical significance may be eligible.)
Pregnant or breastfeeding women.
Patients with clinically significant cardiovascular disease within the past 12 months (e.g., congestive heart failure, symptomatic coronary artery disease, arrhythmias, myocardial infarction).
Patients whose toxicities from prior anticancer therapy have not recovered to baseline or ≤ Grade 2.
Patients who received any prior anticancer therapy within 14 days or localized radiotherapy within 7 days before the first dose of the study drug.
Patients with a known hypersensitivity to the study drugs.
Any condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hye Ryun KIM | Contact | 82-2-2228-8125 | nobelg@yuhs.ac | |
| Chang Gon kim | Contact | 82-10-9162-1729 | inspector@yuhs.ac |
| Name | Affiliation | Role |
|---|---|---|
| Hye Ryun Kim | Severance Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yonsei University Health System, Severance Hospital | Seoul | South Korea |
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| ID | Term |
|---|---|
| D055752 | Small Cell Lung Carcinoma |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| C568606 | PM 01183 |
| D017239 | Paclitaxel |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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| Paclitaxel | Drug | Administered IV at 80 mg/m² on Days 1 and 8 every 21-day cycle until disease progression or unacceptable toxicity. |
|
| PFS2 for the Two Regimens (Progression-Free Survival 2) | Progression-Free Survival (PFS) is defined as the time from the first administration date of the investigational drug in the clinical trial to the date of the second disease progression (PD) during subsequent chemotherapy, death, or death from any cause, whichever occurs first. PFS will be analyzed using the Kaplan-Meier method. The secondary progression-free survival will be analyzed in the efficacy evaluable population. If progression status cannot be assessed due to death during follow-up, end of survival confirmation, withdrawal of consent, or other reasons, the last disease assessment date will be censored. | End of trial (approximately 3 years) |
| Overall survival (OS) | Overall Survival (OS) is assessed based on the date of first administration of the investigational drug and the survival status at the time of analysis. OS is defined as the time from the first administration of the investigational drug to death from any cause. OS will be analyzed in the safety analysis set and presented using Kaplan-Meier plots. The number of events, median survival time (calculated from Kaplan-Meier curves), and the proportion of subjects without events will be summarized at 6, 12, and 18 months. The numbers and proportions of subjects who have died, are alive, lost to follow-up, or withdrawn consent will also be appropriately summarized. | End of trial (approximately 3 years) |
| Disease control rate (DCR) | Disease Control Rate (DCR) is defined as the percentage of subjects whose best overall response (BOR), including both intracranial and extracranial responses, is complete response (CR), partial response (PR), responding, or stable disease (SD). DCR will be summarized in the efficacy evaluable population. DCR will be presented along with two-sided 95% confidence intervals, assuming a normal distribution | End of trial (approximately 3 years) |
| Duration of response (DoR) | Duration of Response (DoR) is defined as the time from the date of first recorded confirmed response to the date of disease progression or death, whichever occurs first (the same as a PFS event). The start of response is defined as the most recent visit date at which a confirmed PR or CR was observed. For subjects who achieve a response but do not experience disease progression, DoR is calculated using the censoring time of PFS. DoR will be analyzed in the subset of the efficacy evaluable population whose best overall response is a confirmed CR or PR. For subjects who respond to treatment, DoR will be summarized, and the number of subjects with DoR exceeding 3, 6, 9, and 12 months will be presented. Kaplan-Meier plots and median DoR (calculated from Kaplan-Meier curves) will also be presented. | End of trial (approximately 3 years) |
| Post-crossover progression-free survival (PFS) | Progression-free survival (PFS) will be evaluated in subjects who were randomized to the control arm (paclitaxel) and subsequently crossed over to receive at least one dose of lurbinectedin monotherapy after confirmed disease progression during paclitaxel treatment. PFS will be analyzed using the Kaplan-Meier method and presented with two-sided 95% confidence intervals. Prespecified subgroup analyses will be performed according to prior paclitaxel response status (CR/PR versus SD/PD) and prior PFS duration (≥3 months versus <3 months). | End of trial (approximately 3 years) |
| Post-crossover overall survival (OS) | Overall survival (OS) will be evaluated in subjects who were randomized to the control arm (paclitaxel) and subsequently crossed over to receive at least one dose of lurbinectedin monotherapy after confirmed disease progression during paclitaxel treatment. OS will be analyzed using the Kaplan-Meier method and presented with two-sided 95% confidence intervals. Prespecified subgroup analyses will be performed according to prior paclitaxel response status (CR/PR versus SD/PD) and prior PFS duration (≥3 months versus <3 months). | End of trial (approximately 3 years) |
| Number of participants with treatment-related adverse events | Treatment-related adverse events will be assessed in all subjects receiving at least one dose of study treatment and graded according to NCI CTCAE. The number and percentage of participants experiencing at least one treatment-related adverse event will be reported. | End of trial (approximately 3 years) |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |