2022-502975-45-00招募中3 期
Randomized, Controlled, Open-label, Phase III Study of Lurbinectedin in Combination with Doxorubicin versus Doxorubicin Alone as First-line Treatment in Patients with Metastatic Leiomyosarcoma (SaLuDo)
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 258
- 试验地点
- 63
- 主要终点
- 1. PFS by IRC is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death).
研究概览
简要总结
The primary objective of this III study is to evaluate whether the combination of lurbinectedin plus doxorubicin given as first line treatment for metastatic leiomyosarcoma (LMS) prolongs the progression-free survival (PFS) by Independent Review Committee(IRC) when compared to doxorubicin administered as a single agent.
研究设计
- 分配方式
- Randomized
- 主要目的
- Phase IIb/III
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Voluntary signed and dated written informed consent of the patient, obtained before any study-specific procedure.
- •Age ≥ 18 years.
- •Histologically confirmed diagnosis of metastatic LMS, in patients not candidates for curative resection.
- •Radiologically measurable disease according to the RECIST v.1.
- •No previous systemic therapy for metastatic disease (i.e., first-line setting) and no previous anthracyclines. Note: Prior chemotherapy (without anthracycline) in the context of adjuvant or neoadjuvant therapy is allowed. Prior line/s of hormone therapy in the adjuvant/metastatic setting are also allowed.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤
- •Adequate hematological, renal, metabolic and hepatic function: a) Hemoglobin ≥ 9.0 g/dL [patients may have received prior red blood cell (RBC) transfusion]; absolute neutrophil count (ANC) ≥ 2.0 x 109/L, and platelet count ≥ 100 x 109/L. b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN). c) Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN if total bilirubin is > ULN. d) Albumin ≥ 3.0 g/dL. e) Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault’s formula). f) Left ventricular ejection fraction (LVEF) > 50% assessed by multiple-gated acquisition scan (MUGA), echocardiography (ECHO) or cardiac magnetic resonance imaging (MRI).
- •Wash-out periods: a) At least three weeks since last prior systemic treatment. b) At least three weeks since last prior major surgery and one week since last prior minor surgery (port placement is excluded from this wash-out period). c) At least two weeks since last prior radiotherapy.
- •Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure up to seven months after treatment discontinuation. Valid methods to determine the childbearing potential, adequate contraception and requirements for WOCBP partners are described in APPENDIX
- •Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.
排除标准
- •Prior treatment with anthracyclines, lurbinectedin or trabectedin.
- •Limitation of the patient’s ability to comply with the treatment or to follow-up the protocol.
- •Patients in whom rapid tumor shrinkage is needed (e.g., when a tumor is close to a critical structure).
- •Women who are pregnant or breast feeding and fertile patients (men and women) who are not using a highly effective method of contraception.* * Women of childbearing potential (WOCBP) must agree to use a highly effective contraception method to avoid pregnancy during the course of the trial (and for at least seven months after the last infusion). Fertile male patients must agree to refrain from fathering a child or donating sperm during the trial and for four months after the last infusion. Valid methods to determine childbearing potential, adequate contraception and requirements of WOCBP partners are described in APPENDIX
- •Known low grade leiomyosarcoma (i.e., grade I).
- •Known hypersensitivity to any of the components of the i.v. formulation of lurbinectedin or doxorubicin.
- •Concomitant diseases/conditions: a) History of cardiac disease: myocardial infarction or angina within the last year prior to enrollment; severe valvular disease; or symptomatic arrhythmia despite ongoing treatment. b) Patients with any immunodeficiency, including those known to be infected by human immunodeficiency virus (HIV). c) Known chronic active hepatitis or cirrhosis. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR. d) Active uncontrolled infection. e) Any other major illness (including severe cardiovascular disease) or risk factors that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study.
- •Use of strong inducers of CYP3A activity within two weeks prior to the first infusion of lurbinectedin.
- •Prior irradiation of a RECIST v.1.1 target lesion if only one target lesion is available, unless progression of this lesion has been confirmed.
- •Known myopathy (history of resolved steroid-induced myopathy is allowed).
- •History of malignancies other than LMS within 3 years prior to enrollment, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, non-muscle-invasive urothelial carcinomas, ductal carcinoma in situ, or stage I uterine cancer. Prior malignancies should have received curative treatment and should remain in remission. The Investigator should ensure, based on histology and/or clinical information, that the current metastatic sites are leiomyosarcoma and not recurrence of the original malignancy.
研究组 & 干预措施
lurbinectedin
Experimental
Participants receiving lurbinectedin
干预措施: lurbinectedin (Drug)
结局指标
主要结局
1. PFS by IRC is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death).
1. PFS by IRC is defined as the time from the date of randomization to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death).
2. If the patient is lost to follow-up before disease progression (PD), PFS will be censored at the date of last tumor assessment.
2. If the patient is lost to follow-up before disease progression (PD), PFS will be censored at the date of last tumor assessment.
3. If the patient receives further antitumor therapy before PD, PFS will be censored at the last tumor assessment performed before the start of new antitumor therapy. In the event of a patient with at least two missing visits before PD, PFS will be censored at the date of the last prior tumor assessment.
3. If the patient receives further antitumor therapy before PD, PFS will be censored at the last tumor assessment performed before the start of new antitumor therapy. In the event of a patient with at least two missing visits before PD, PFS will be censored at the date of the last prior tumor assessment.
次要结局
- 2A PFS by IA is defined as the time from the date of registration to the date of documented progression per RECIST v.1.1 or death (regardless of the cause of death).
- 3. ORR by IRC and IA is defined as the percentage of patients with a response, either complete (CR) or partial (PR), according to the RECIST v.1.1.
- 4. Duration of response (DoR) by IRC and IA will be calculated from the date of first documentation of response per RECIST v.1.1 (CR or PR, whichever comes first) to the date of documented PD or death. The censoring rules defined for PFS will be used for DoR.
- 5. Clinical Benefit Rate (CBR) by IRC and IA is defined as objective response plus stable disease (SD) ≥ 6 months according to the RECIST v.1.1.
- 6. PFS on next-line therapy (PFS2) by IA is defined as the time from the date of randomization to the date of progression on next line treatment or death (regardless of the cause of death), whichever occurs first. In case of no event, follow-up of the patient will be censored at the date of last news.
- 1. Key secondary endpoint: • Overall survival (OS) will be calculated from the date of randomization to the date of death (death event) or last contact (in this case, survival will be censored on that date).Other Secondary Endpoints:
- 7. Treatment safety profile: AEs, serious adverse events (SAEs) and laboratory abnormalities will be coded by the Medical Dictionary for Regulatory Activities (MedDRA), graded according to the NCI-CTCAE v.5 and analyzed. Dose delays or reductions required due to treatment-related AEs, and reasons for treatment discontinuations will also be assessed.
- 8. Patient-reported outcomes (PRO): To measure the quality of life of patients, the EORTC QLQ-C30 questionnaire will be analyzed.
- 9 Subgroup analyses: Subgroup analyses of efficacy and safety profiles in the Experimental arms and the Control arm will be performed.
- 10. Plasma PK of lurbinectedin, doxorubicin and its metabolite doxorubicinol will be evaluated using a sparse sampling scheme. Details will be given in a population PK analysis plan, and results will be presented in a separate report.
- 11. PK/PD correlation: Population PK correlations of exposure to lurbinectedin, doxorubicin and its metabolite doxorubicinol with safety will be explored. Details will be given in specific population PK/PD analysis plans, and results will be presented in separate reports.
- 2B If the patient is lost to follow-up before PD, PFS will be censored at the date of last tumor assessment. If the patient receives further antitumor therapy before PD, PFS will be censored at the last tumor assessment performed before the start of new antitumor therapy.
- 12A Pharmacogenomics (PGx): The mutational status and the expression levels of potential predictive factors of response and/or resistance to lurbinectedin and doxorubicin treatment, or to doxorubicin alone will be analyzed from available tumor and/or blood samples obtained before, during and at the end of treatment (either during the EOT visit, or as soon as possible during the follow-up period).
- 12B Their correlation with the clinical response and outcome after treatment will be assessed. This analysis will be performed in those patients who signed the ICF for the PGx substudy.
- 2C In the event of a patient with at least two missing visits before PD, PFS will be censored at the date of the last prior tumor assessment otherwise
研究者
Clinical Development Oncology Unit
Scientific
Pharma Mar S.A.
研究点 (63)
Loading locations...
相似试验
进行中（未招募）
1 期
Effect of Lurbinectedin (PM01183) on Cardiac Repolarization (QTc Duration) in Patients with Solid TumorsEUCTR2015-000206-18-ESPharmaMar S.A., Sociedad Unipersonal25
已完成
1 期
Study of Lurbinectedin (PM01183) in Combination With Capecitabine in Patients With Metastatic Breast Cancer (MBC), Pancreatic Cancer (PC) or Metastatic Colorectal Cancer (CRC).Metastatic Breast CancerMetastatic Colorectal CancerPancreatic CancerNCT02210364PharmaMar81
已完成
1 期
Pharmacokinetic Study of Lurbinectedin in Combination With Irinotecan in Patients With Selected Solid TumorsAdvanced Solid TumorsSoft Tissue Sarcoma (Excluding GIST)Endometrial CarcinomaEpithelial Ovarian CarcinomaMesotheliomaGastroenteropancreatic Neuroendocrine TumorGastric CarcinomaPancreatic AdenocarcinomaColorectal CarcinomaNeuroendocrine TumorsGlioblastomaSCLCNCT02611024PharmaMar316
进行中（未招募）
3 期
Study of Lurbinectedin in Combination With Doxorubicin Versus Doxorubicin Alone as First-line Treatment in Participants With Metastatic Leiomyosarcoma (SaLuDo)LeiomyosarcomaNCT06088290PharmaMar469
进行中（未招募）
1 期
Clinical Trial of Lurbinectedin (PM01183) in Selected Advanced Solid Tumors.Selected Advanced Solid Tumors.MedDRA version: 18.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 100000004864EUCTR2014-003773-42-SEPharma Mar S.A. Sociedad Unipersonal225