临床试验/NCT02784171

NCT02784171已完成2 期

A Phase II/III Randomized Study of Pembrolizumab in Patients With Advanced Malignant Pleural Mesothelioma

Canadian Cancer Trials Group56 个研究点分布在 3 个国家目标入组 520 人开始时间: 2016年11月11日最近更新: 2024年12月10日

适应症

干预措施

试验速览

阶段: 2 期
状态: 已完成
发起方: Canadian Cancer Trials Group
入组人数: 520
试验地点: 56
主要终点: Phase II: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

Pembrolizumab is a new type of drug for mesothelioma (immunotherapy). Laboratory tests show that this drug works by helping improve the body's immune response to help fight cancer. Pembrolizumab may help the immune system to recognize cancer cells and slow down the growth and/or spreading of cancer.

详细描述

The purpose of this study is to find out what effects a new drug, pembrolizumab has on this type of cancer and if it can offer better results than standard pemetrexed and platinum-based chemotherapy alone. This study will also look at side effects and how the treatments impact quality of life

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patients must have histologically confirmed malignant pleural mesothelioma. Patients must be eligible to receive standard chemotherapy with pemetrexed and cisplatin and have no contraindications to standard chemotherapy.
•Patients must have unresectable advanced and/or metastatic disease, incurable by standard therapies.
•All patients must have a cellular tumour block from their primary or metastatic tumour available and consent to release the block/recently cut slides for correlative analyses (See Section 11.0) and the centre/pathologist must have agreed to the submission of the specimen(s).
•Presence of radiologically documented disease. At least one site of disease must be unidimensionally measurable as follows:
•CT scan (with slice thickness of ≤ 5 mm): ≥ 10 mm --> longest diameter
•Physical exam (using calipers): ≥ 10 mm
•Lymph nodes by CT scan ≥ 15 mm --> measured in short axis
•All radiology studies must be performed within 21 days prior to registration (exception: within 28 days if negative).
•Age ≥ 18 years.
•ECOG performance status 0 or
•Previous Therapy
•Cytotoxic Chemotherapy:
•Patients must not have received prior chemotherapy for any stage of advanced/metastatic disease.
•Patients who received previous (neo)adjuvant cisplatin-based systemic chemotherapy must have received the last dose of chemotherapy at least 12 months before registration. Please contact CCTG PRIOR to randomization for such patients.
•Other Anti-Cancer Therapy:
•Patients may not have received targeted small molecule therapy, immunotherapies and viral therapies, biologic therapies and angiogenesis inhibitors for advanced/metastatic disease, or any prior immunotherapy for any stage of disease.
•Patients may have had prior radiation therapy, but NOT to the thorax unless clear disease progression has been demonstrated and confirmed with CCTG. A minimum of 28 days must have elapsed between the end of radiotherapy and registration onto the study. Radiation must have involved < 30% of functioning bone marrow and there must be measurable disease outside the previously irradiated area (patients whose sole site of disease (for example pleural rind) is in a previously irradiated area are ineligible UNLESS there is evidence of progression, or new lesions have been documented, in the irradiated field). Please contact CCTG PRIOR to randomization if the patient has received prior thoracic radiation. Patients must have recovered from any acute toxic effects from radiation prior to registration.
•Previous Surgery:
•Previous major surgery is permitted provided that it has been at least 28 days prior to patient registration and that wound healing has occurred.
•Lab Requirements:
•Absolute neutrophils ≥ 1.5 x 10^9/L
•Platelets ≥ 100 x 10^9/L
•Hemoglobin ≥ 90 g/L
•Bilirubin ≤ 1.5 x ULN (upper limit of normal)
•AST and ALT ≤ 2.5 x ULN
•Serum creatinine < 1.25 x ULN or Creatinine clearance ≥ 50 mL/min
•Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
•Patients must be accessible for treatment, response assessment and follow-up. Patients registered on this trial must be treated and followed at the participating centre.
•In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization.
•Women/men of childbearing potential must have agreed to use two highly effective contraceptive methods during the study and for six months after discontinuation.
•Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires.

排除标准

•Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (at doses more than 10 mg prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first and any dose of trial treatment.
•Has active autoimmune disease that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or history of allogeneic transplantation. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
•Must not have received a live vaccine within 30 days of planned start of study therapy.
•Patients with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
•Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction including cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects) or who have had unstable angina congestive heart failure or myocardial infarction within the previous year. Patients with a significant cardiac history, this includes hypertension, even if controlled, should have a LVEF ≥ 50%.
•Patients with a history of other malignancies unless having undergone curative therapy (i.e. resection, radiation, etc) and do not require concurrent anticancer therapy.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab or any of the other chemotherapy agents.
•Concurrent treatment with other investigational drugs or anti0cancer therapy.
•Patients with serious illness or medical condition that would not permit the patient to be managed according to the protocol including, but not limited to:
•History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements.
•Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) [note: testing in asymptomatic patients is not required] or tuberculosis).
•Known history of, or any evidence of active, non-infectious pneumonitis.
•Any other medical conditions that might be aggravated by treatment.
•Serious or non-healing wound, ulcer, or bone fracture.
•Patients with evidence of interstitial lung disease.
•Patients with severe/uncontrollable tumor pain that requires radiation prior to starting on systemic therapy.
•Pregnant or lactating women. (N.B.: All women of childbearing potential must have a negative pregnancy test within 72 hours prior to registration).

研究组 & 干预措施

Arm B - Cisplatin/Pemetrexed/Pembrolizumab

Active Comparator

Pembrolizumab 200 mg* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles

干预措施: Pemetrexed (Drug)

Arm A - Cisplatin/Pemetrexed

Active Comparator

Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles

干预措施: Cisplatin (Drug)

Arm A - Cisplatin/Pemetrexed

Active Comparator

Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles

干预措施: Pemetrexed (Drug)

Arm B - Cisplatin/Pemetrexed/Pembrolizumab

Active Comparator

Pembrolizumab 200 mg* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles

干预措施: Cisplatin (Drug)

Arm B - Cisplatin/Pemetrexed/Pembrolizumab

Active Comparator

Pembrolizumab 200 mg* IV Day 1 over 30 min every 21 days for a total of 2 years Pemetrexed 500 mg/m2 IV Day 1 every 21 days for 6 cycles Cisplatin 75 mg/m2 IV Day 1 every 21 days for 6 cycles

干预措施: Pembrolizumab (Drug)

Arm C - Pembrolizumab (Phase II only)

Active Comparator

Pembrolizumab 200 mg* IV 30 min Day 1 every 21 days for a total of 2 years

干预措施: Pembrolizumab (Drug)

结局指标

主要结局

Phase II: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression

时间窗: PFS was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.

PFS was calculated for all randomized patients from the day of randomization until the first observation of disease progression (date of objective relapse or progression of Relapse/Progression Report) or death due to any cause (recorded in Date/Cause of Death Section of Death Report).

Phase III: Overall Survival Defined as Time From Randomization to the Date of Death From Any Cause

时间窗: Survival was monitored continuously throughout the study and during follow-up. Patients were evaluated for each cycle, 4 weeks after discontinuation, every 12 weeks until progression, and then every 24 weeks until death, an average of 16.2 months.

Overall survival was defined as time from the day of randomization to death for patients died. For patients still alive at time of data-cutoff for analysis, it was censored at the last day the patients were known alive as the last of all dates .

次要结局

Phase III: Progression Free Survival Measured as Time From Randomization to First Observation of Objective Disease Relapse or Progression(PFS was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.)
Phase III: Objective Response Rate(Response was monitored continuously, with assessments every 6 weeks for 3 visits, then every 12 weeks, 4 weeks post-discontinuation, every 12 weeks until progression, and every 24 weeks until death, over an average of 16.2 months.)

研究者

发起方

Canadian Cancer Trials Group

申办方类型

Network

责任方

Sponsor

研究点 (56)

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