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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)

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ClinicalTrials.gov Identifier: NCT05153239
Recruitment Status : Recruiting
First Posted : December 10, 2021
Last Update Posted : April 12, 2024
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Tracking Information
First Submitted Date  ICMJE November 29, 2021
First Posted Date  ICMJE December 10, 2021
Last Update Posted Date April 12, 2024
Actual Study Start Date  ICMJE July 22, 2022
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2021)
Overall survival [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2024)
  • Progression-free survival by IRC (Independent Review Committee) [ Time Frame: 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.
  • Progression-free survival by IA (Investigator Assessment) [ Time Frame: 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 by IRC [ Time Frame: From the date of randomization to the date of death or last contact, up to 39 months ]
    Overall response rate (ORR) will be the percentage of patients with complete or partial response as 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 response rate by IA [ Time Frame: From the date of randomization to the date of death or last contact, up to 39 months ]
    Overall response rate (ORR) will be the percentage of patients with complete or partial response as 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 [ Time Frame: 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 [ Time Frame: 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 by IRC [ Time Frame: 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 6 months by IA [ Time Frame: 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 by IRC [ Time Frame: 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
  • Progression-free survival rate at 12 months by IA [ Time Frame: 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 by IRC [ Time Frame: 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.
  • Duration of response by IA [ Time Frame: 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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2021)
  • Progression-free survival [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
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.
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 and pretreated 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Multicenter, open-label, randomized, controlled
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Irinotecan
    Irinotecan 75 mg/m² intravenously Days 1 & 8 q3wk
  • Drug: Lurbinectedin
    Lurbinectedin 3.2 mg/m² will be administered intravenously on Day 1 q3wk
    Other Name: PM01183
  • Drug: Irinotecan
    For patients aged <70 years: irinotecan 350 mg/m² intravenously Day 1 q3wk For patients aged ≥70 years: irinotecan 300 mg/m² intravenously Day 1 q3wk
  • Drug: Topotecan
    Topotecan 2.3 mg/m² oral or 1.5 mg/m² intravenously Days 1-5 q3wk
  • Drug: Lurbinectedin
    Lurbinectedin 2.0 mg/m² will be administered intravenously on Day 1 q3wk
    Other Name: PM01183
Study Arms  ICMJE
  • Experimental: Lurbinectedin
    Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)
    Intervention: Drug: Lurbinectedin
  • 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)
    Interventions:
    • Drug: Irinotecan
    • Drug: Lurbinectedin
  • Active Comparator: Control arm

    Best Investigator's choice prior to randomization between:

    • Irinotecan on Day 1 q3wk
    • Topotecan on Days 1-5 q3wk
    Interventions:
    • Drug: Irinotecan
    • Drug: Topotecan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2021)
705
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2025
Estimated Primary Completion Date June 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Voluntary written informed consent of the patient obtained before any study-specific procedure
  2. Age≥18 years
  3. Histologically or cytologically confirmed diagnosis of SCLC.
  4. 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)
  5. 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)
  6. 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
  7. Eastern Cooperative Oncology Group (ECOG) PS ≤ 2
  8. Adequate hematological, renal, metabolic and hepatic function:

    1. 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.
    2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN).
    3. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN.
    4. Albumin ≥ 3.0 g/dL.
    5. Calculated creatinine clearance (CrCL) ≥ 30 mL/min (using Cockcroft and Gault's formula).
  9. 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.
  10. Prior radiotherapy (RT): At least two weeks since completion of prophylactic cranial irradiation (PCI), and to any other site not previously specified.
  11. 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.

Exclusion Criteria:

  1. Platinum-naïve patients or patients pretreated with more than one prior chemotherapy regimen (including patients re-challenged with same initial regimen).
  2. Prior treatment with lurbinectedin, trabectedin, PM14, or topoisomerase I inhibitors (irinotecan, topotecan, etc.).
  3. Active or untreated CNS metastases and/or carcinomatous meningitis.
  4. 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.
  5. Concomitant diseases/conditions:

    1. History or presence of unstable angina, myocardial infarction, congestive heart failure, or clinically significant valvular heart disease within last year.
    2. Symptomatic arrhythmia or any uncontrolled arrhythmia requiring ongoing treatment.
    3. Ongoing chronic alcohol consumption or cirrhosis with Child-Pugh score B or C.
    4. Known Gilbert's disease.
    5. Active uncontrolled infection. Serious non-healing wound, ulcer or bone fracture. Presence of external drainages.
    6. 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.
    7. 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.
    8. 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.
    9. Limitation of the patient's ability to comply with the treatment or to follow the protocol.
    10. Documented or suspected invasive fungal infections requiring systemic treatment within 12 weeks of randomization.
    11. Known human immunodeficiency virus (HIV) infection.
    12. Any past or present chronic inflammatory colon and/or liver disease, past intestinal obstruction, pseudo or subocclusion or paralysis.
    13. Evident symptomatic pleural or cardiac effusion rapidly increasing and/or necessitating prompt local treatment within seven days.
    14. 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).
  6. RT in more than 35% of the bone marrow.
  7. History of previous bone marrow and/or stem cell transplantation and allogenic transplant.
  8. 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.
  9. Impending need for RT (e.g., painful bone metastasis and/or risk of spinal cord compression).
  10. History of allergy or hypersensitivity to any of the study drugs or any of their excipients.
  11. Women who are pregnant or breast feeding and fertile patients (men and women) who are not able to use a highly effective method of contraception
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: José Antonio Lopez-Vilariño, MD 0034 91 823 4564 jalopez-vilarino@pharmamar.com
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   Denmark,   France,   Georgia,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Poland,   Romania,   Spain,   Switzerland,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05153239
Other Study ID Numbers  ICMJE PM1183-C-008-21
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party PharmaMar
Original Responsible Party Same as current
Current Study Sponsor  ICMJE PharmaMar
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PharmaMar
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP