2022-500988-12-00招募中2 期
Phase II, open label, single arm study of PembrolizumAb combiNeD with cisplatin or carbOplatin and etoposide in treatment naïve advanced meRkel cell cArcinoma (MCC) (PANDORA Trial).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 3
- 主要终点
- ORR, that will be defined as the percentage of patients achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria
研究概览
简要总结
To assess efficacy of pembrolizumab combined with chemotherapy as first line treatment in patients with MCC
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
- •Patients must be capable of giving signed informed consent
- •No previous systemic therapy for advanced disease
- •Patients with treated or asymptomatic brain metastases may be enrolled
- •Women of childbearing potential must use 2 effective methods of contraception with a failure rate of less than 1% per year, during the entire study treatment period and for a period of 5 months after the last dose of study drug, or agree to practice true abstinence, when this is in line with the preferred and us usual lifestyle of the subject. They must have a negative serum pregnancy test during the screening period.
- •Adequate haematological function defined by white blood cell (WBC) count ≥2,500/mm 3 with absolute neutrophil count (ANC) ≥1,500/mm 3, platelet count ≥ 100,000/mm 3 and haemoglobin ≥9 g/dL
- •Adequate hepatic function defined by a total bilirubin ≤ 1.5 x the upper limit of normal (ULN) range (except subjects with Gilbert Syndrome), serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN (≤ 5 if liver function test elevations are due to liver metastases)
- •Adequate renal function defined by a serum creatinine ≤ 1.5 x ULN or an estimated creatinine clearance of ≥ 30 mL/minute for patients with creatinine levels above institutional limits (if using the Cockcroft Gault formula)
- •Stable medical condition, including the absence of acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before registration, and otherwise noted in other inclusion/exclusion criteria
- •Ability to comply with protocol requirements
- •Patients must be ≥18 years of age at the time of signing the ICF
- •Locally advanced, relapsed or metastatic MCC stage IIIB-IV according to American Joint Committee on Cancer (AJCC) TNM Staging Classification for Merkel Cell Carcinoma (8th ed. 2017)
- •Histologically confirmed diagnosis of MCC.
- •Availability of tumor sample (obtained from core biopsy or surgical specimen) is mandatory for PD L1 expression assessment and biomolecular characterization.
- •Life expectancy ≥ 3 months
- •Measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
排除标准
- •Prior treatment with pembrolizumab or any other immunotherapy agents (anti PD 1, anti PD L1, anti PD L2, anti CD137, anti CTLA 4 antibodies, or any other antibody or drug specifically targeting T cell costimulatory immune checkpoint pathways)
- •Vaccination within 4 weeks of the first dose and while on trial is prohibited except for administration of inactivated vaccines
- •Unwilling or unable to comply with the protocol or cooperate fully with the investigator and site personnel
- •Prior treatment with chemotherapy for advanced MCC with the exception for subjects who received adjuvant or neoadjuvant therapy. They are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the onset of metastatic disease.
- •Known hypersensitivity to pembrolizumab, carboplatin, cisplatin and/or etoposide
- •Concurrent anticancer treatment, immune therapy, or cytokine therapy, except for erythropoietin
- •Major surgery for any reason within 4 weeks from registration and/or if the subject has not fully recovery from the surgery within 4 weeks of treatment start
- •Subjects receiving immunosuppressive agents such as steroids for any reason should be tapered of these drugs before initiation of the trial treatment. Low dose corticosteroid therapy will be allowed.
- •Known severe hypersensitivity reactions to chimeric or monoclonal antibodies, fusion proteins
- •Patients with untreated, symptomatic and/or progressive brain metastases, or with carcinomatous meningitis. Subjects with brain metastases are eligible if metastases have been treated and there is no clinical evidence of progression
- •History of active autoimmune diseases. Subjects with diabetes mellitus type I, hypothyroidism only requiring hormone replacement or controlled hyperthyroidism, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •Other concurrent neoplasms requiring active treatment
- •Adjuvant radiotherapy is permitted if ended ≥ 6 months before trial enrollment.
- •Prior organ transplantation, including allogenic stem cell transplantation
- •Any medical condition, within 6 months before receiving the first dose of study drug, considered relevant by Investigator.
- •Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
- •Serious infection within 14 days before the first dose of study drug
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- •Active tuberculosis
- •Pregnancy or breastfeeding
结局指标
主要结局
ORR, that will be defined as the percentage of patients achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria
ORR, that will be defined as the percentage of patients achieving complete response (CR) or partial response (PR) according to RECIST 1.1 criteria
次要结局
- Incidence of Serius Adverse Events (SAE)
- Incidence and severity of Immune-mediated Adverse Events (imAE)
- Incidence and severity of Adverse Events (AEs) according to NCI Common Terminology criteria Adverse Event (CTCAE), version 5.0
- Overall Survival (OS) that will be measured from the date of starting therapy to the date of death by any cause
- Progression Free Survival (PFS) that will be measured from the date of starting therapy to the date of disease progression or death.
- Duration of Response (DOR) that will be measured from the date of the first response to disease progression or death in those patients who achieved a CR o PR during study treatment
研究者
Clinical trial contact point
Scientific
Fondazione IRCCS Istituto Nazionale Dei Tumori
研究点 (3)
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