Lurbinectedin Plus Paclitaxel Versus Paclitaxel in Patients With Previously Treated Small Cell Lung Cancer (LUPINE)
Lurbinectedin in Combination With Paclitaxel Versus Paclitaxel for Patients With Previously Treated Small Cell Lung Cancer: Randomized, Phase II, Open-label, Multi-center, Prospective Trial(LUPINE)
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Hye Ryun Kim
- 電話番号：82-2-2228-8125
- メール：nobelg@yuhs.ac
研究連絡先のバックアップ
- 名前：Chang Gon kim
- 電話番号：82-10-9162-1729
- メール：inspector@yuhs.ac
研究場所
-
-
-
Seoul、韓国
- Yonsei University Health System, Severance Hospital
-
コンタクト：
- Hye Ryun Kim
- 電話番号：82-2-2228-8125
- メール：nobelg@yuhs.ac
-
コンタクト：
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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:
- Patients who failed treatment within 6 months after curative-intent chemotherapy are considered as having failed first-line therapy.
- For platinum-sensitive patients, participation in the third-line cohort is allowed after re-treatment with a platinum-based regimen as second-line therapy (limited-stage).
- For platinum-resistant patients, participation in the second-line cohort is allowed (limited-stage).
- 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:
- HBsAg-positive patients may be eligible if HBV DNA is negative or appropriate antiviral therapy is being administered.
- HCV antibody-positive patients may be eligible if HCV RNA is negative or the patient has been cured after treatment.
- 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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Combination therapy of Lurbinectedin and Paclitaxel
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. |
Administered IV at 2.2 mg/m² on Day 1 every 21-day cycle until disease progression or unacceptable toxicity.
Administered IV at 80 mg/m² on Days 1 and 8 every 21-day cycle until disease progression or unacceptable toxicity.
|
|
アクティブコンパレータ：Paclitaxel monotherapy
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.
|
Administered IV at 80 mg/m² on Days 1 and 8 every 21-day cycle until disease progression or unacceptable toxicity.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Objective Response Rate (ORR)
時間枠：End of trial(approximately 3years)
|
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)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression-Free Survival (PFS) according to RECIST v1.1
時間枠：End of trial (approximately 3 years)
|
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)
|
|
PFS2 for the Two Regimens (Progression-Free Survival 2)
時間枠：End of trial (approximately 3 years)
|
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)
時間枠：End of trial (approximately 3 years)
|
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)
時間枠：End of trial (approximately 3 years)
|
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)
時間枠：End of trial (approximately 3 years)
|
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)
時間枠：End of trial (approximately 3 years)
|
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)
時間枠：End of trial (approximately 3 years)
|
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
時間枠：End of trial (approximately 3 years)
|
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)
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Hye Ryun Kim、Severance Hospital
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
がん、小細胞肺の臨床試験
-
Taichung Veterans General Hospital完了心毒性 | 非小細胞肺癌（MeSH用語：Carcinoma, Non-Small-Cell Lung） | 薬物関連の副作用および有害反応（MeSH用語） | EGFRチロシンキナーゼ阻害剤台湾
-
Fondazione del Piemonte per l'Oncologia募集乳がん | 卵巣がん | 結腸直腸がん | 黒色腫 (皮膚がん) | 非小細胞肺癌（MeSH用語：Carcinoma, Non-Small-Cell Lung）イタリア