Clinical Trial of Lurbinectedin as Single-agent or in Combination With Irinotecan Versus Topotecan or Irinotecan in Patients With Relapsed Small-cell Lung Cancer (LAGOON)
- Conditions
- Small Cell Lung Cancer (SCLC)
- Interventions
- Registration Number
- 2024-513559-34-00
- Lead Sponsor
- Pharma Mar S.A.
- Brief Summary
To determine whether there is a difference in terms of overall survival (OS) between lurbinectedin as single agent (Group A) or the combination of lurbinectedin with irinotecan (Group B) versus Investigator’s Choice (topotecan or irinotecan) (Group C) in patients with relapsed SCLC after failure of one prior platinum-containing chemotherapy line.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 517
Voluntary written informed consent of the patient obtained before any study-specific procedure.
Prior radiotherapy (RT): At least two weeks since completion of prophylactic cranial irradiation (PCI), and to any other site not previously specified.
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. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last investigational medicinal product (IMP) dose.
Age ≥ 18 years.
Histologically or cytologically confirmed diagnosis of SCLC.
One prior line of platinum-containing chemotherapy with/without anti-PD-1 or anti-PD-L1 (Note: at least 70% of patients included in the study have to be pretreated with anti-PD-1 or anti-PD-L1).
Chemotherapy-free interval (CTFI, time from the last dose of first-line platinum-containing chemotherapy to the occurrence of progressive disease) ≥ 30 days (independent of the immunotherapy maintenance, if applicable).
Patients with history of CNS metastases can participate provided they are pretreated and radiologically stable (i.e., without evidence of progression) for at least 4 weeks by repeated imaging (note: repeated imaging should be performed during study screening), asymptomatic, and without requirement of steroid treatment for at least 7 days before the first dose of study treatment.
Eastern Cooperative Oncology Group (ECOG) PS ≤ 2.
Adequate hematological, renal, metabolic and hepatic function: a) Hemoglobin ≥ 9.0 g/dL [patients may have received prior red blood cell (RBC) transfusion, if clinically indicated]; absolute neutrophil count (ANC) ≥ 2.0 x 10^9/L, and platelet count ≥ 100 x 10^9/L. b) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN. c) Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN. d) Albumin ≥ 3.0 g/dL. e) Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault’s formula).
At least three weeks since last prior antineoplastic treatment and recovery to grade ≤ 1 from any adverse event (AE) related to previous anticancer treatment (excluding sensory neuropathy, immune-related hypothyroidism, anemia, asthenia and alopecia, all grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.
Platinum-naïve patients or patients pretreated with more than one prior chemotherapy regimen (including patients re-challenged with same initial regimen).
History of allergy or hypersensitivity to any of the study drugs or any of their excipients.
Women who are pregnant or breast feeding and fertile patients (men and women) who are not using a highly effective method of contraception (see inclusion criterion No.11).
Prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors (irinotecan, topotecan, etc.).
Active or untreated CNS metastases and/or carcinomatous meningitis.
Patients with limited-stage disease who are candidates for local or regional therapy, including PCI, thoracic RT or both, must have been offered that option and completed treatment or refused it prior to randomization.
Concomitant diseases/conditions: a) History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year. b) Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment. c) Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C. d) Known Gilbert´s disease. e) Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture. Presence of external drainages. f) Ongoing, treatment-requiring, non-neoplastic chronic liver disease of any origin. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen (HBsAg) 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. Subjects taking hepatitis-related antiviral therapy within six months prior to the first dose of study drugs will also be excluded. g) Intermittent or continuous oxygen requirement within two weeks prior to randomization. Patients with confirmed or suspected diagnosis of diffuse interstitial lung disease or pulmonary fibrosis. h) Patients with a second invasive malignancy treated with chemotherapy and/or RT. Patients with a previous malignancy that was completely resected with curative intention three or more years prior to randomization, except treated in situ carcinoma of the cervix, basal or squamous cell skin carcinoma, and in situ transitional cell bladder carcinoma and who has been continuously in remission since then will be permitted. i) Limitation of the patient’s ability to comply with the treatment or to follow the protocol. j) Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization. k) Known human immunodeficiency virus (HIV) infection. l) Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or sub-occlusion or paralysis. m) Evident symptomatic pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days. n) Any other major illness that, in the Investigator’s judgment, will substantially increase the risk associated with the patient’s participation in this study (e.g., COVID-19 disease).
RT in more than 35% of the bone marrow.
History of previous bone marrow and/or stem cell transplantation and allogenic transplant.
Patient has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of inactivated vaccines is allowed.
Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description lurbinectedin lurbinectedin Participants receiving lurbinectedin
- Primary Outcome Measures
Name Time Method Overall survival (OS) Overall survival (OS)
- Secondary Outcome Measures
Name Time Method OS rate at 12 and 24 months and PFS rate at 6 and 12 months by IRC/IA OS rate at 12 and 24 months and PFS rate at 6 and 12 months by IRC/IA
Duration of response (DoR) by IRC/IA Duration of response (DoR) by IRC/IA
Treatment safety profile Treatment safety profile
Patient-reported outcomes (PRO) Patient-reported outcomes (PRO)
Progression-free survival (PFS) by Independent Review Committee (IRC)/Investigator's Assessment (IA) Progression-free survival (PFS) by Independent Review Committee (IRC)/Investigator's Assessment (IA)
Overall response rate (ORR) by IRC/IA Overall response rate (ORR) by IRC/IA
Subgroup analyses: Subgroup analyses of efficacy and safety Subgroup analyses: Subgroup analyses of efficacy and safety
Plasma pharmacokinetics (PK) of lurbinectedin, irinotecan and its metabolite SN-38 Plasma pharmacokinetics (PK) of lurbinectedin, irinotecan and its metabolite SN-38
PK/PD correlation PK/PD correlation
Pharmacogenomics (PGx) Pharmacogenomics (PGx)
Trial Locations
- Locations (100)
Lillebaelt Hospital
🇩🇰Vejle, Denmark
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Sygehus Soenderjylland Soenderborg
🇩🇰Soenderborg, Denmark
Specjalistyczna Praktyka Lekarska Sławomir Mandziuk
🇵🇱Lublin, Poland
Uniwersytecki Szpital Kliniczny W Bialymstoku
🇵🇱Bialystok, Poland
Szpitale Pomorskie Sp. z o.o.
🇵🇱Gdynia, Poland
Szpital Specjalistyczny W Prabutach Sp. z o.o.
🇵🇱Prabuty, Poland
Mruk-Med I Sp. z o.o.
🇵🇱Rzeszow, Poland
Specjalistyczny Szpital Onkologiczny Nu-Med Sp. z o.o.
🇵🇱Tomaszow Mazowiecki, Poland
Humanitas Mirasole S.p.A.
🇮🇹Rozzano, Italy
Scroll for more (90 remaining)Lillebaelt Hospital🇩🇰Vejle, DenmarkLisbeth BertelsenSite contact+4579406811Lisbeth.Bertelsen@rsyd.dk