PEMBROLIZUMAB for Small cell lung cancer (extensive-stage)

Inclusion criteria

• {"criterion_text":"- Histologically or cytologically documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration."}
• {"criterion_text":"- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of lenvatinib placebo and up to 180 days after the last dose of chemotherapeutic agents: -Refrain from donating sperm PLUS either: -Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR -Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause ) as detailed below: # Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant."}
• {"criterion_text":"- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: o Is not a WOCBP OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab and 30 days post-lenvatinib and up to 180 days post last dose of chemotherapeutic agents, whichever occurs last. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention. - A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention. - If a urine test cannot be confirmed as negative , a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive."}
• {"criterion_text":"- Have voluntarily agreed to participate by giving written consent for the study prior to any specific protocol procedures."}
• {"criterion_text":"- Have adequate organ function."}
• {"criterion_text":"- ES-SCLC, stage IV disease by the American Joint Committee on Cancer, 8th Edition criteria, [T any, N any, M1a, M1b, M1c], or T3–4 due to multiple lung nodules that are too extensive or tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan."}
• {"criterion_text":"- Have at least one lesion that meets criteria for being measurable, as defined by RECIST 1.1."}
• {"criterion_text":"- Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for biomarker assessment."}
• {"criterion_text":"- Be male or female ≥18 years of age inclusive, on the day of signing informed consent."}
• {"criterion_text":"- Have a life expectancy of at least 3 months from the study start."}
• {"criterion_text":"- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7 days prior to the first dose of study intervention"}

Exclusion criteria

• {"criterion_text":"- Has received any prior therapy for the treatment of SCLC."}
• {"criterion_text":"- Has received a live vaccine or live-attenuated vaccine within 30 days prior to FDS."}
• {"criterion_text":"- Is currently participating inor has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to FDS."}
• {"criterion_text":"- Has an active autoimmune disease or inflammatory disorder that has required systemic treatment in the past 2 years."}
• {"criterion_text":"- Has a diagnosis of immunodeficiency or is taking chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to FDS."}
• {"criterion_text":"- Has known history of a second malignancy other than SCLC, unless potentially curative treatment has been completed with no evidence of malignancy for at least 3 years since the initiation of that therapy."}
• {"criterion_text":"- Poor controlled hypertension despite appropriate treatment."}
• {"criterion_text":"- Participants with proteinuria >1+ on urine dipstick testing/urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 g/24 hours will be ineligible."}
• {"criterion_text":"- Has a prolongation of QTc interval of >480 msec."}
• {"criterion_text":"- Has a known history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia , drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan"}
• {"criterion_text":"- Uncontrolled intercurrent active infection at the time of enrollment requiring systemic therapy."}
• {"criterion_text":"- Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy while on study."}
• {"criterion_text":"- Has a known history of HIV infection."}
• {"criterion_text":"- Has a known history of Hepatitis B or active Hepatitis C virus infection"}
• {"criterion_text":"- Has a known history of active tuberculosis."}
• {"criterion_text":"- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study."}
• {"criterion_text":"- Has known psychiatric or substance abuse disorders."}
• {"criterion_text":"- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment."}
• {"criterion_text":"- Prior allogeneic bone marrow transplantation or solid organ transplant."}
• {"criterion_text":"- Any gastrointestinal condition that would affect the absorption of Lenvatinib"}
• {"criterion_text":"- Has active hemoptysis or major arterial thromboembolic event within 2 weeks prior to the first dose of study intervention."}
• {"criterion_text":"- Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction, CVA, or cardiac arrhythmia associated with hemodynamic instability."}
• {"criterion_text":"- Active CNS metastases and/or carcinomatous meningitis as determined per CT or MRI during screening. Participants with previously treated brain metastases may participate only if they satisfy the following: # Completed treatment at least 14 days prior to the first dose of study (FDS). # Are clinically and radiologically stable # Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to enrollment, if all other criteria are met."}
• {"criterion_text":"- Has a history of a severe hypersensitivity reaction to treatment with another monoclonal Ab or has a known hypersensitivity to lenvatinib, pembrolizumab, carboplatin or etoposide and/or any of its excipients."}
• {"criterion_text":"- Has a clinically active diverticulitis, inflammatory bowel disease, intra-abdominal abscess, gastrointestinal obstruction and/or abdominal carcinomatosis."}
• {"criterion_text":"- Has a history of a gastrointestinal perforation within 6 months before FDS."}
• {"criterion_text":"- Has preexisting Grade ≥ 3 gastrointestinal or non-gastrointestinal fistula."}
• {"criterion_text":"- Has serious nonhealing wound, ulcer, or bone fracture within 28 days before FDS."}
• {"criterion_text":"- Has any major hemorrhage or venous thromboembolic events within 3 months before FDS."}
• {"criterion_text":"- Poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease."}
• {"criterion_text":"- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor"}
• {"criterion_text":"- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for ≥ 1 week prior to enrollment."}
• {"criterion_text":"- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures"}
• {"criterion_text":"- Has known history of, or active, neurologic paraneoplastic syndrome of autoimmune nature"}
• {"criterion_text":"- Radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel."}
• {"criterion_text":"- Has had major surgery within 4 weeks prior to FDS."}

Primary endpoints

• {"endpoint_text":"- Part 1: * Safety and tolerability Dose-limiting toxicities (DLTs), adverse events (AEs) and study intervention discontinuations due to AEs. Part 2: • Progression-free Survival (PFS) per RECIST 1.1 assessed by investigator","definition_or_measurement_approach":"Part 1 measured by DLTs, adverse events (AEs) and study intervention discontinuations due to AEs; Part 2 measured as Progression-free Survival (PFS) per RECIST 1.1 assessed by investigator."}
• {"endpoint_text":"- Part 2: • Progression-free Survival (PFS) per RECIST 1.1 assessed by investigator","definition_or_measurement_approach":"Progression-free Survival (PFS) per RECIST 1.1 assessed by investigator."}

Secondary endpoints

• {"endpoint_text":"- Part 1 (for patients treated at part 2): Objective response per RECIST 1.1 based on investigator","definition_or_measurement_approach":"Objective response per RECIST 1.1 based on investigator assessment."}
• {"endpoint_text":"- Part 1 (for patients treated at part 2): Duration of response (DOR) per RECIST 1.1 based on investigator","definition_or_measurement_approach":"Duration of response (DOR) per RECIST 1.1 based on investigator assessment."}
• {"endpoint_text":"- Part 1 (for patients treated at part 2): Overall Survival","definition_or_measurement_approach":"Overall survival measured from randomization/enrollment to death (as reported)."}
• {"endpoint_text":"- Part 2: Objective response per RECIST 1.1 based on investigator","definition_or_measurement_approach":"Objective response per RECIST 1.1 based on investigator assessment."}
• {"endpoint_text":"- Part 2: DOR per RECIST 1.1 based on investigator","definition_or_measurement_approach":"Duration of response (DOR) per RECIST 1.1 based on investigator assessment."}
• {"endpoint_text":"- Part 2: Safety and tolerability","definition_or_measurement_approach":"Assessed by adverse events, discontinuations and related safety assessments."}
• {"endpoint_text":"- Part 2: Overall Survival","definition_or_measurement_approach":"Overall survival measured as time to death (as reported)."}

Spain

Earliest CTIS Part Ii Submission Date

14-03-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

769

Number Of Sites

18

Number Of Participants

46

Primary sponsor

Full Name

Fundacion GECP

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain