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)

Sponsor

PharmaMar (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05153239

Collaborator

(none)

705

Enrollment

Locations

Arms

33.3

Anticipated Duration (Months)

7.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Multicenter, open-label, randomized, controlled phase III clinical trial to evaluate and compare the activity and safety of two experimental arms consisting of lurbinectedin as single agent (Group A) or the combination of lurbinectedin with irinotecan (Group B) versus Investigator's Choice (topotecan or irinotecan) as control arm (Group C), in Small-cell Lung Cancer (SCLC) patients who failed one prior platinum-containing line.

Condition or Disease	Intervention/Treatment	Phase
Relapsed Small Cell Lung Cancer	Drug: Irinotecan Drug: Lurbinectedin Drug: Irinotecan Drug: Topotecan Drug: Lurbinectedin	Phase 3

Detailed Description

Approximately 705 Adult SCLC patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 who have failed one prior platinum-containing line with CTFI ≥ 30 days and controlled asymptomatic Central Nervous System metastases will be enrolled and assigned to each treatment arm.

Central randomization will be implemented; patients will be assigned to each treatment arm at a 1:1:1 ratio.

An Independent Data Monitoring Committee (IDMC) will oversee the conduct of the study. The IDMC should have access to unblinded efficacy and safety data throughout the trial to enable timely and informed judgments about risks and benefits.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

705 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Multicenter, open-label, randomized, controlledMulticenter, open-label, randomized, controlled

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Multicenter, Open-label, Phase III Study of Lurbinectedin Single-Agent or Lurbinectedin in Combination With Irinotecan Versus Investigator's Choice (Topotecan or Irinotecan) in Relapsed Small Cell Lung Cancer Patients (LAGOON Trial)

Actual Study Start Date :

Jul 22, 2022

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lurbinectedin Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)	Drug: Lurbinectedin Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 q3wk Other Names: PM01183
Experimental: Lurbinectedin plus Irinotecan Patients will consecutively receive the following q3wk (every three weeks = one treatment cycle): Irinotecan (Day 1 and Day 8) Lurbinectedin (Day 1)	Drug: Irinotecan Irinotecan 75 mg/m² intravenously Days 1 & 8 q3wk Drug: Lurbinectedin Lurbinectedin 2.0 mg/m² will be administered intravenously on Day 1 q3wk Other Names: PM01183
Active Comparator: Control arm Best Investigator's choice prior to randomization between: Irinotecan on Day 1 q3wk Topotecan on Days 1-5 q3wk	Drug: Irinotecan Irinotecan 350 mg/m² intravenously Day 1 q3wk Drug: Topotecan Topotecan 2.3 mg/m² oral or 1.5 mg/m² intravenously Days 1-5 q3wk

Arm

Intervention/Treatment

Experimental: Lurbinectedin

Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)

Drug: Lurbinectedin

Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 q3wk

Other Names:

PM01183

Experimental: Lurbinectedin plus Irinotecan

Patients will consecutively receive the following q3wk (every three weeks = one treatment cycle): Irinotecan (Day 1 and Day 8) Lurbinectedin (Day 1)

Drug: Irinotecan

Irinotecan 75 mg/m² intravenously Days 1 & 8 q3wk

Drug: Lurbinectedin

Lurbinectedin 2.0 mg/m² will be administered intravenously on Day 1 q3wk

Other Names:

PM01183

Active Comparator: Control arm

Best Investigator's choice prior to randomization between: Irinotecan on Day 1 q3wk Topotecan on Days 1-5 q3wk

Drug: Irinotecan

Irinotecan 350 mg/m² intravenously Day 1 q3wk

Drug: Topotecan

Topotecan 2.3 mg/m² oral or 1.5 mg/m² intravenously Days 1-5 q3wk

Outcome Measures

Primary Outcome Measures

Overall survival [From the date of randomization to the date of death or last contact, up to 39 months]
Overall survival (OS) will be calculated from the date of randomization to the date of death or last contact (in this case, survival will be censored on that date).

Secondary Outcome Measures

Progression-free survival [From the date of randomization to the date of progressive disease, death or last tumor assessment or further anticancer treatment, up to 39 months]
Progression-free survival (PFS) will be calculated from the date of randomization to the date of documented progression per RECIST v.1.1 (Progressive disease is declared when there is an increase in sum of target disease ≥ 20%) or death (regardless of the cause of death). If the patient receives further antitumor therapy, withdraws from the study, or is lost to follow-up before progressive disease (PD), PFS will be censored at the date of last evaluable tumor assessment before the date of subsequent antitumor therapy.
Overall response rate [From the date of randomization to the date of death or last contact, up to 39 months]
Overall response rate (ORR) will be the best response obtained in any evaluation according to RECIST v.1.1. Progressive disease is declared when there is an increase in sum of target disease ≥ 20%, stable disease when the change is > -30% and ≤ 20%, partial response when there is a decrease in sum of target disease ≥ 30%, and complete response when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.
Overall survival rate at 12 months [At 12 months]
Overall survival rate at 12 months is defined as the percentage of people who are still alive at 12 months after randomization.
Overall survival rate at 24 months [At 24 months]
Overall survival rate at 24 months is defined as the percentage of people who are still alive at 24 months after randomization.
Progression-free survival rate at 6 months [At 6 months]
Progression-free survival rate at 6 months is defined as the percentage of people who remain free from progression at 6 months after randomization
Progression-free survival rate at 12 months [At 12 months]
Progression-free survival rate at 12 months is defined as the percentage of people who remain free from progression at 12 months after randomization
Duration of response [From the date of first documentation of complete or partial response to the date of documented progression disease, death or last contact, up to 39 months]
Duration of response (DoR) will be calculated from the date of first documentation of response per RECIST v.1.1 (complete or partial response, whichever occurs first) to the date of documented PD or death. Progressive disease is declared when there is an increase in sum of target disease ≥ 20%, stable disease when the change is > -30% and ≤ 20%, partial response when there is a decrease in sum of target disease ≥ 30%, and complete response when all lesions have disappeared or all lesions have disappeared and all nodal disease is < 10 mm each.
Patient-reported outcomes [At baseline and every six weeks (± one week) until end of treatment, up to 39 months]
To measure the quality of life of patients, the Lung Cancer Symptom Scale (LCSS) questionnaire will be analyzed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Voluntary written informed consent of the patient obtained before any study-specific procedure
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 Central Nervous System (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:
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.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN.
Albumin ≥ 3.0 g/dL.
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, anemia, asthenia and alopecia, all grade ≤ 2) according to the National Cancer InstituteCommon Terminology Criteria for Adverse Events (NCICTCAE) v.5.
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 six 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.

Exclusion Criteria:

Platinum-naïve patients or patients pretreated with more than one prior chemotherapy regimen (including patients re-challenged with same initial regimen).
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:
History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.
Known Gilbert's disease.
Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture. Presence of external drainages.
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.
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.
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.
Limitation of the patient's ability to comply with the treatment or to follow the protocol.
Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization.
Known human immunodeficiency virus (HIV) infection.
Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.
Evident symptomatic pulmonary fibrosis or interstitial pneumonitis, pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
Active COVID-19 disease (this includes positive test for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or nasal swabs by PCR).
Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study.
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 killed vaccines is allowed.
Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
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 able to use an effective method of contraception

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duly Health and Care	Joliet	Illinois	United States	60435
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina	United States	28374
4	The Chris Obrien Lifehouse	Camperdown	New South Wales	Australia	2050
5	BRICC - Ballarat Health Services	Ballarat Central	Victoria	Australia	3350
6	Box Hill Hospital Eastern Health Clinical School	Box Hill	Victoria	Australia	3128
7	Antwerp University Hospital	Edegem	Antwerp	Belgium	2650
8	Algemeen Ziekenhuis AZ Klina - Borstkliniek	Brasschaat		Belgium	2930
9	Grand Hopital de Charleroi GHdC - Hopital Saint Joseph	Charleroi		Belgium	6000
10	Centre Hospitalier Chretien CHC - MontLegia	Liège		Belgium	4000
11	CHR de la Citadelle	Liège		Belgium	4000
12	CHU Liege	Liège		Belgium	4000
13	Az Sint Maarten Mechelen	Mechelen		Belgium	2800
14	Centre Hospitalier Universitaire (CHU) Ambroise Pare	Mons		Belgium	7000
15	Multiprofile Hospital for Active Treatment - Uni Hospital OOD Department of Medical Oncology	Sofia	Dianabad	Bulgaria	1797 NPZ
16	Complex Oncology Center - Plovdiv EOOD, First Department of Medical Oncology and Oncological Diseases in Gastroenterology	Plovdiv		Bulgaria	4000
17	Specialized hospital for active treatment of oncological diseases	Sofia		Bulgaria	1233
18	Multiprofile Hospital for Active Treatment Serdika EOOD Second Department of Medical Oncology	Sofia		Bulgaria	1303
19	McGill University Health Centre (MUHC)	Montréal		Canada	H4A 3J1
20	Hopital Jean Minjoz	Besancon		France	25030
21	AssAP-HP - Hopital Ambroise-Pare	Boulogne-Billancourt		France	92100
22	Hopital Morvan CHU de Brest	Brest		France	29200
23	CHU de Caen - Hopital Cote de Nacre	Caen		France	14033
24	Centre Hospitalier Intercommunal de Creteil (CHIC)	Créteil		France	94000
25	APHM - Hopital Nord	Marseille		France	13015
26	Gustave Roussy	Villejuif		France	94805
27	High Technology Hospital Medcenter	Batumi		Georgia	6000
28	Todua Clinic	Tbilisi		Georgia	112
29	New Hospitals	Tbilisi		Georgia	114
30	Institute Of Clinical Oncology	Tbilisi		Georgia	156
31	JSC Evex Hospitals "Caraps Medline"	Tbilisi		Georgia	179
32	LTD Cancer Research Centre	Tbilisi		Georgia	186
33	LungenClinic Grosshansdorf	Großhansdorf	Schleswig Holstein	Germany	22927
34	Charite - Universitaetsmedizin Berlin	Berlin		Germany	13353
35	Klinikum Bremen Ost	Bremen		Germany	28325
36	Asklepios Fachklinik München-Gauting	Gauting		Germany	82131
37	Krankenhaus Martha-Maria Halle gGmbH	Halle (saale)		Germany	06120
38	Thoraxclinic Heidelberg GmbH	Heidelberg		Germany	69126
39	Klinikum Kassel - Medizinische Klinik IV	Kassel		Germany	34125
40	Universitaetsmedizin Mannheim	Mannheim		Germany	68167
41	Staedtisches Klinikum München - Bogenhausen	München		Germany	81925
42	A.O. SS. Antonio e Biagio e Cesare Arrigo di Alessandria	Alessandria		Italy	15121
43	Clinica Oncologica	Ancona		Italy	60126
44	IRCCS Centro di Riferimento Oncologico	Aviano		Italy	33081
45	IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola Malpighi Oncologia medica	Bologna		Italy	40138
46	Azienda Ospedaliera Univ. Policlinico G Rodolico San Marco	Catania		Italy	95125
47	A.O. Santa Croce e Carle, Ospedale Carle	Cuneo		Italy	12100
48	AOU Careggi	Florence		Italy	50134
49	ASL 3 Genovese Oncologia Medica Villa Scassi	Genova		Italy	16149
50	Universita degli Studi della Campania Luigi Vanvitelli	Napoli		Italy	80138
51	Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano		Italy	10043
52	Oncologia Medica II Istituto Oncologico Veneto IRCCS	Padova		Italy	35128
53	Azienda USL di Piacenza	Piacenza		Italy	29121
54	Irccs-Crob	Rionero In Vulture		Italy	85028
55	IFO Regina Elena	Roma		Italy	00128
56	Policlinico Uni. Campus Bio-Medico	Roma		Italy	00128
57	Azienda Ospedaliera Univ. Senese Policlinico Le Scotte	Siena		Italy	53100
58	ASST Valtellina e Alto Lario Ospedale di Sondrio ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio	Sondrio		Italy	23100
59	ASST Sette Laghi	Varese		Italy	21100
60	II Klinika Chorob Pluc i Gruzlicy	Białystok		Poland	15-569
61	Szpitale Pomorskie Sp. z o.o., Oddzial Onkologii K	Gdynia		Poland	81-519
62	Specjalistyczna Praktyka Lekarska Slawomir Mandziuka	Lublin		Poland	20-093
63	Szpital Specjalistyczny w Prabutach Sp. z o.o	Prabuty		Poland	82-550
64	Mrukmed. Lekarz Beata Madej-Mruk i Partner. Sp.p	Rzeszów		Poland	35-021
65	Specjalistyczny Szpital Onkologiczny NU-MED sp. Z	Tomaszów Mazowiecki		Poland	97-200
66	Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu	Toruń		Poland	87-100
67	Wojewódzkie Wielospecjalistyczne Centrum Onkologii	Łódź		Poland	93-513
68	Institut Català d Oncologia (ICO) - Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
69	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria	Spain	39008
70	Complejo Hospitalario Materno-Insular de Gran Canaria	Las Palmas De Gran Canaria	Gran Canaria	Spain	35016
71	Complexo Hospitalario Universitario De Vigo (CHUVI) - Hospital Xeral	Vigo	Pontevedra	Spain	36312
72	Hospital Teresa Herrera C.H.U.A.	A Coruña		Spain	15009
73	Hospital HM Nou Delfos	Barcelona		Spain	08023
74	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
75	Hospital Universitario Reina Sofía	Córdoba		Spain	14004
76	Hospital Universitario Lucus Augusti	Lugo		Spain	27003
77	Hospital Universitario La Paz	Madrid		Spain	28006
78	Hospital General Universitario Gregorio Marañón	Madrid		Spain	28007
79	Clínica Universidad de Navarra	Madrid		Spain	28027
80	MD Anderson Cancer Center	Madrid		Spain	28033
81	Hospital Universitario Ramón y Cajal	Madrid		Spain	28034
82	Hospital Clínico San Carlos	Madrid		Spain	28040
83	Hospital Universitario Fundación Jimenez Díaz	Madrid		Spain	28040
84	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
85	Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
86	Hospital Regional Universitario Málaga Hospital Civil	Málaga		Spain	29010
87	Hospital Universitario Virgen del Rocío	Sevilla		Spain	41013
88	Hospital Universitari i Politècnic La Fe	Valencia		Spain	46026
89	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47003
90	Hospital Clínico Universitario Lozano Bleza	Zaragoza		Spain	50009
91	Belfast Health and Social Care Trust	Belfast		United Kingdom	BT9 7AB
92	The Princess Alexandra Hospital	Harlow		United Kingdom	CM20 1QX
93	University Hospitals of Leicester NHS Trust	Leicester		United Kingdom	LE1 5WW
94	Guys and St Thomas NHS Foundation Trust	London		United Kingdom	SE1 9RT
95	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX