Lenvatinib for Malignant pleural mesothelioma

Inclusion criteria

• {"criterion_text":"- Histologically or cytologically diagnosed malignant pleural mesothelioma, age at least 18 years\n- A male participant who agrees to use contraception as detailed in age and reproductive status breastfeeding (see 4.3.1.2 Age and reproductive status) (contraceptive methods appendix G)\n- Anticipated life expectancy of ≥3 months\n- Progressive disease after at least 1 and maximal 2 prior systemic treatment lines: - Cohort 1: patients in which one of the lines contains a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM - Cohort 2: patients with only nivolumab-ipilimumab immunotherapy as first line treatment for unresectable MPM. No prior chemotherapy.\n- Measurable disease. At least one measurable lesion according to Modified RECIST 1.1 for pleural mesothelioma. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions\n- WHO-ECOG performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to date of allocation\n- Adequate organ function, including : Hematological Hematologisch o Absolute neutrophil count ≥ 1.5 x 109/l o Platelets≥ 150 x 109/l o Hemoglobin ≥6,0 mmol/l (9.0g/dL) Hepatic o Total serum bilirubin ≤ 1.5 times within the upper limits of normal (ULN) (except for Gilbert disease) o ASAT and ALAT < 2.5x ULN o AP (alkaline phosphatases) < 5x ULN (unless bone metastases are present in the absence of any liver disease). Renal o Proteinuria ≤ Grade 2 NCI CTCAE 5.0. Subjects having >1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subject with urine protein ≥1 g/24-hour will be ineligible. o Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 40mL/min Coagulation o INR ≤ 1.5 x ULN unless patients is receiving anticoagulant therapy as long as INR is within therapeutic range of intended use of anticoagulants\n- Ability to understand the study and give signed informed consent (or legally acceptable representative if applicable) prior to beginning of protocol specific procedures including the approval of the thoracoscopy or transthoracic pleural biopsy before the first treatment cycle and an optional biopsy before the third treatment cycle\n- Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in hypertensive medication within 1 week before the cycle 1/day1.\n- A female is eligible if she is not pregnant and not breastfeeding (see 4.3.1.2. Age and reproductive status) (contraceptive methods appendix G)\n- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception to avoid pregnancy during treatment and for 120 days a"}

Exclusion criteria

• {"criterion_text":"- Presence of clinically relevant treatment-related toxicity from previous chemotherapy, targeted therapy and/or radiotherapy. Note: Participates must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤2 neuropathy may be eligible\n- Symptomatic and/or hemorrhagic brain metastases\n- Known hypersensitivity to trial drug or their excipients\n- Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger. Hormone replacement like eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc. are permitted. Inhaled or topical steroids are not considered a form of systemic treatment.\n- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug\n- History of (non-infectious) pneumonitis that required steroids and no current pneumonitis\n- Known history of Human Immunodeficiency Virus (HIV) and/or known history of active TB (Bacillus Tuberculosis) and/or kwon history of hepatitis B or known active Hepatitis C virus\n- Known other malignancy that is progressing or has required active treatment during the previous two years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded\n- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n- Active uncontrolled infection, severe cardiac dysfunction (i.e. unstable angina, history of myocardial infarction within the past 12 months prior to screening, congestive heart failure > NYHA II, serious cardiac arrhythmia), unstable peptic ulcer, unstable diabetes mellitus or other seriously disabling condition\n- Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with another agent agents direct to another stimulatory or co-inhibitory T-cell receptor (eg CTLA-4, OC-40, CD137) or TKI or antibody targeting angiogenesis in the first cohort. Patients who have been treated with autologous tumor cell vaccination (eg. Dendritic cell-based immunotherapy) will be eligible.\n- Concomitant administration to any other experimental drugs under investigation ≤ 4 weeks prior to first admission of pembrolizumab- lenvatinib\n- Prior radiotherapy within 2 weeks before start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids as therapy for radiation induced toxicities. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.\n- Major injuries and/or surgery within the past 4 weeks prior to first study dose with incomplete wound healing\n- History of clinically significant hemorrhagic or thromboembolic event within 6 months of screening\n- Known inherited predisposition to bleeding or thrombosis\n- Live vaccine within 4 weeks prior to the first dose of study drug"}

Primary endpoints

• {"endpoint_text":"- The proportion of patients with an objective response, defined by Modified RECIST 1.1 criteria for malignant pleural mesothelioma (see appendix C), determined by the local physician and compare ORR with historical controls.","definition_or_measurement_approach":"Objective response rate (ORR) defined by Modified RECIST 1.1 criteria for malignant pleural mesothelioma; determined by the local physician and compared with historical controls."}

Secondary endpoints

• {"endpoint_text":"- Extent of exposure, AEs, SAEs, treatment related AEs (TRAEs/SAEs) , AE’s leading to discontinuation of study drug(s)/withdrawal, fatal TRAEs and deaths. Other AEs that the investigator deemed important to report and reasons for discontinuation of study drug(s). AE grading will be performed by NCI Common Terminology Criteria for Adverse Events Version 5.0.","definition_or_measurement_approach":"Safety endpoints: adverse events, serious adverse events, treatment-related AEs, discontinuations, fatal TRAEs; AE grading by NCI CTCAE v5.0."}
• {"endpoint_text":"- To estimate the disease control rate (DCR) progression-free survival (PFS) determined by defined by ModifiedRECIST 1.1 criteria for malignant pleural mesothelioma Duration of response (DOR) (all determined by the local physician) and overall survival (OS).","definition_or_measurement_approach":"DCR, PFS, DOR determined by Modified RECIST 1.1 criteria for malignant pleural mesothelioma as assessed by the local physician; OS measured as overall survival."}
• {"endpoint_text":"- To describe the DCR, ORR, DOR and PFS by independent radiological review","definition_or_measurement_approach":"Independent radiological review to assess DCR, ORR, DOR and PFS."}

Netherlands

Earliest CTIS Part Ii Submission Date

16-09-2024

Latest Decision Or Authorization Date

24-09-2024

Processing Time Days

8

Number Of Sites

1

Number Of Participants

58

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"Merck Sharp & Dohme (MSD)","duties_or_roles":"Source of monetary support","organisation_type":""}