2024-516545-39-01招募中2 期
Changes in the tumour microenvironment after intravenous or intradermal administration of anti-CTLA-4 in combination with anti-PD1 treatment in patients with melanoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- T cell subset frequencies (as percentage of parent), and systemic activation (determined as a 50 % or greater increase in expression of inducible T-cell costimulator (ICOS/CD278)) in PBMCs CD4+/CD8+ T cells at baseline and on-treatment in both groups.
研究概览
简要总结
To determine the systemic immunological effects of a single dose of 20 mg ipilimumab locally administered i.d. in combination with i.v. standard of care nivolumab compared to systemic standard of care i.v. administration of ipilimumab and nivolumab as determined with the fre-quency and functionality of tumour-specific T cells and Tregs in peripheral blood cells.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Patient must be of age ≥ 18 years, and have a histologically confirmed diagnosis of locally advanced, surgically incurable, or metastatic cutaneous melanoma.
- •Written and signed informed consent.
- •European Cooperative Oncology Group (ECOG)/World Health Organisation (WHO) performance status of 0 or
- •Patient must be eligible for anti-PD-1 treatment with nivolumab (group 1) or with ipili-mumab + nivolumab (group 2) according to the treating physician.
- •Patient must be eligible for anti-PD-1 treatment with nivolumab (group 1) or with ipili-mumab + nivolumab (group 2) according to the treating physician.
- •Patients must have a life expectancy of 3 months or greater.
- •Patients must have measurable disease (according to RECIST v1.1) with at least one cutaneous metastasis. Note: measurable disease defined as: at least 1 visceral or nodal/soft tissue melanoma lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 10 mm as measured by CT-scan or MRI. Lymph nodes must measure ≥ 15 mm in their short axis to be considered measurable by CT-scan or MRI.
- •Adequate bone marrow, hepatic, renal and coagulation function (to be conducted within 7 days prior to start therapy, during the baseline period): o Leukocyte count ≥ 3,5 × 109 / L o Platelets ≥ 100 × 109 / L. o Total bilirubin ≤ 3 × the upper limit of normal (ULN). o Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 3.0 × ULN; except patients with documented liver metastases ASAT and/or ALAT ≤ 5.0 × ULN. o (Estimated) creatinine clearance ≥ 45 mL/min/1,73 m
- •o Albumin ≥ 30g / L o LDH ≤ 2 x ULN
- •Women of childbearing potential (WOCBP) must use contraception (see § 9.2.1) during the study and for 23 weeks after the last dose of nivolumab.
- •Men who are sexually active with WOCBP must use contraception (see § 9.2.1) during the study plus 7 months after the last dose of nivolumab.
排除标准
- •Primary uveal or mucosal melanoma.
- •Patient has used systemic corticosteroids to treat inflammatory or autoimmune symp-toms within 15 days or other immunosuppressive drugs within 30 days prior to screen-ing. Exceptions: o Patients that require intermittent use of inhalation or topical corticosteroids are eligible for the study. o Patient has received acute, low-dose, systemic immunosuppressant medica-tions (e.g., a one-time dose of dexamethasone for nausea) that, in the opinion of the Investigator, will not compromise protocol objectives.
- •Patient has had treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor agents) within 2 weeks prior to baseline.
- •Patient has had treatment with systemic immunostimulatory agents (including but not limited to interferons [IFNs] or interleukin-2 [IL-2]) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to baseline.
- •Known history or evidence of immunodeficiency states (e.g., organ transplant, leukaemia, human immunodeficiency virus (HIV), hepatitis B, hepatitis C or known acquired immunodeficiency syndrome (AIDS)). NOTE: Testing for HIV must be performed at sites were mandated locally.
- •Patient has had any major surgery within 4 weeks prior to enrolment or major surgery is scheduled during the study, with the exception of procedures that are part of the study site IIS.
- •Patient has any safety laboratory test results (clinical chemistry, haematology, and urinalysis) that, in the opinion of the Investigator, could compromise patient safety or protocol objectives.
- •Patient has any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the ICI treatment, or that may affect the interpretation of the results or render the patient at high risk from complications.
- •Patient has history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins or known allergy to the study IMP ingredients and/or the proposed ICI therapy.
- •Pregnancy or breastfeeding.
- •Patient has a history of alcohol or drug abuse within the last year.
- •Prior treatment with CTLA-4 inhibitor or agonist, or anti-PD1, except for adjuvant nivolumab > 6 months ago.
- •Currently participating in or has participated in a study of an investigational agent within 30 days of baseline or has not recovered from adverse events due to agents adminis-tered more than 4 weeks earlier, except A Phase 1a/1b, Multi-Centre, Open-Label, Dose-Escalation and Dose-Expansion Study in Patients with Solid Tumor Malignancies to Evaluate GEH200520 Injection / GEH200521 (18F) Injection Safety and Tolerability, Positron Emission Tomography Imaging, Pharmacokinetics, and Changes in Imaging after Treatment; NCT05629689, EU Trial number: 2024-515218-42-
- •For any reason, patient is considered by the local investigator to be an unsuitable candidate to participate in this study.
- •Prior radiotherapy is permitted except on RECIST v1.1 target lesions within 2 weeks of start of trial treatment. Irradiated lesions without progression before start of treatment cannot be target lesions. Note: Patients must have recovered from all radiation-related toxicities, and not require corticosteroids.
- •Patient has 12-lead ECG significant findings during screening, per Investigator’s assessment.
- •History of another malignancy (that is progressing or requires active treatment) within the previous 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cancer that has undergone potentially curative therapy.
- •Patient has a confirmed active SARS-CoV-2 infection.
- •Patient has serious non-malignant disease or conditions that, in the opinion of the Investigator, could compromise patient safety or protocol objectives.
- •Patient has brain or bone-marrow metastasis that, in the opinion of the Investigator, could compromise patient safety or protocol objectives.
- •Active systemic infections requiring therapy, or signs or symptoms of a systemic infec-tion within two weeks prior to baseline.
结局指标
主要结局
T cell subset frequencies (as percentage of parent), and systemic activation (determined as a 50 % or greater increase in expression of inducible T-cell costimulator (ICOS/CD278)) in PBMCs CD4+/CD8+ T cells at baseline and on-treatment in both groups.
T cell subset frequencies (as percentage of parent), and systemic activation (determined as a 50 % or greater increase in expression of inducible T-cell costimulator (ICOS/CD278)) in PBMCs CD4+/CD8+ T cells at baseline and on-treatment in both groups.
次要结局
- Safety of i.d. ipilimumab (group 1 only): Adverse events using Common Terminology Criteria Adverse Events, version 5.0 (CTCAE 5.0), reported as frequency of treatment-related events. Grade 3 or higher will be reported separately.
研究者
Willemien Menke - van der Houven van Oordt
Scientific
Stichting Amsterdam UMC
研究点 (1)
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