NCT03298893已完成1 期
A Phase-I Study of Nivolumab in Association With Radiotherapy and Cisplatin in Locally Advanced Cervical Cancers Followed by Adjuvant Nivolumab for up to 6 Months. NiCOL
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 3
- 主要终点
- rate of occurrence of dose-limiting toxicity (DLT)
研究概览
简要总结
To date, the majority of clinical trials on checkpoint inhibitors have tested these agents as monotherapy, and the next logical step is to evaluate rational therapeutic associations. The aim of the NiCOL study is to assess the safety of nivolumab in association with chemoradiation therapy and to gain initial insight into its efficacy in association with the current standard of care, including chemoradiation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult patients at least 18 years of age;
- •Ability to understand and the willingness to sign a written informed consent document.;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1;
- •Histologically confirmed locally advanced cervical cancer, i.e. FIGO stages IB2 to IVA, squamous-cell carcinoma or adenocarcinoma, with indication for radiotherapy and cisplatin-based chemotherapy with a curative intent as confirmed by a multidisciplinary board including a radiation oncologist. PD-L1 expression on tumor will not be required for inclusion; (staging may include [18F]-fluorodeoxyglucose (FDG) PET-CT and/or para-aortic dissection in accordance with usual practice in each investigational center and at the Investigator's discretion);
- •Disease amenable to biopsy since three tumor samples are mandatory prior to treatment;
- •Laboratory values at Screening must meet the following criteria :
- •neutrophils ≥ 1.0 x 109/L, lymphocytes ≥ 0.5 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 8.0 g/dL, creatinine ≤ 2 times the upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 3 ULN, alanine aminotransferase (ALT) ≤ 3 x ULN, total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN if genetically documented Gilbert's syndrome).
- •For women with child-bearing potential, negative blood or urinary pregnancy test within 24 hours of initiation of nivolumab, as well as appropriate method of contraception throughout the study ;
- •Affiliated to the French Social Security System.
排除标准
- •Metastases (except pelvic and/or para-aortic nodal metastases) ;
- •Peritoneal carcinosis;
- •Sensory or motor neuropathy ≥ grade 2;
- •Active or recent history of known autoimmune disease or recent history of a syndrome that required systemic corticosteroids or immunosuppressive drugs, except for :
- •hydrocortisone, which is permitted at physiological doses;
- •syndromes that would not be expected to recur in the absence of an external trigger, e.g. glomerulonephritis;
- •vitiligo or autoimmune thyroiditis;
- •Type-1 or type-2 diabetes;
- •History of or current immunodeficiency disease, including known history of infection with human immunodeficiency virus;
- •Prior systemic treatment or radiotherapy for cervical cancer;
- •Prior allogeneic stem cell transplantation;
- •Prior immunotherapy, including tumor vaccine, cytokine, anti-CTLA4, anti-PD-1, anti-PD-L1 or similar agents;
- •Any non-oncologic vaccine for prevention of infectious disease within 28 days prior to inclusion, including but not limited to measles, mumps, rubella, chicken pox, yellow fever, seasonal influenza, H1N1, rabies, BCG, and typhoid vaccine;
- •Positive serology for hepatitis B surface antigen;
- •Positive for hepatitis-C ribonucleic acid on polymerase chain reaction;
- •Active infection requiring therapy;
- •History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia or evidence of active pneumonitis on chest CT-scan at Screening;
- •History of malignancy (excepting non-melanoma skin cancer) unless complete remission was achieved at least 3 years prior to inclusion and no additional therapy is required or planned during the study;
- •Underlying medical condition that, in the Investigator's opinion, could render the administration of the study treatment hazardous; additional severe and/or uncontrolled concurrent disease;
- •Concomitant use of other investigational drugs;
- •Pregnancy or breastfeeding.
研究组 & 干预措施
Nivolumab + radiochemotherapy
Experimental
5 weeks of radiochemotherapy + nivolumab followed by 5 months of nivolumab alone
干预措施: Nivolumab Injection (Drug)
Nivolumab + radiochemotherapy
Experimental
5 weeks of radiochemotherapy + nivolumab followed by 5 months of nivolumab alone
干预措施: Cisplatin (Drug)
Nivolumab + radiochemotherapy
Experimental
5 weeks of radiochemotherapy + nivolumab followed by 5 months of nivolumab alone
干预措施: radiotherapy (Radiation)
结局指标
主要结局
rate of occurrence of dose-limiting toxicity (DLT)
时间窗: within 11 weeks after the initiation of treatment.
DLT is defined as any of the following treatment-related adverse events or laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0: * non-hematological toxicity ≥ grade 3; * immune-related adverse event ≥ grade 3; * symptomatic immune-related adverse event ≥ grade 2 resistant to optimal supportive care for \> 7 days; * dosing delay in RT ≥ 1 week due to toxicity related to nivolumab, chemotherapy or RT; * colitis or diarrhea ≥ grade 3.
次要结局
- Incidence of Serious Adverse Events (SAEs) to assess the overall safety profile of the association of nivolumab and pelvic radio-chemotherapy(from the first intake of the IMP until 100 days after the last intake of the IMP)
- Disease Free Survival (DFS)(2 years)
- tumor microenvironment description(2 years)
- Objective Response Rate (ORR)(after the end of RT and before brachytherapy and again up to 2 months after brachytherapy)
- Progression Free Survival (PFS)(2 years)
- Incidence of Adverse Events (AEs) to assess the overall safety profile of the association of nivolumab and pelvic radio-chemotherapy(from the first intake of the IMP until 100 days after the last intake of the IMP)
- ctDNA heterogeneity(baseline, at Weeks 3, 6 and 12 and every 12 weeks up to Week 104)
- validation of molecular alterations detected by molecular analyses(2 years)
- tumor PD-L1 immunohistochemistry(2 years)
研究者
研究点 (3)
Loading locations...
相似试验
已完成
2 期
Nivolumab Combined With Chemoradiotherapy Sparing Concurrent Cisplatin in Nasopharyngeal CarcinomaNasopharyngeal CarcinomaNCT03984357Sun Yat-sen University152
已完成
2 期
NIVOLUMAB Plus IPILIMUMAB and TEMOZOLOMIDE in Microsatellite Stable, MGMT Silenced Metastatic Colorectal CancerMetastatic Colorectal CancerNCT03832621Fondazione IRCCS Istituto Nazionale dei Tumori, Milano135
已完成
1 期
A Study to Compare Nivolumab Drug Product Process D to Nivolumab Drug Product Process C in Participants With Stage IIIa/b/c/d or Stage IV Melanoma After Complete ResectionMelanomaNCT03980314Bristol-Myers Squibb261
终止
2 期
An Investigational Immuno-therapy Study to Test Combination Treatments in Patients With Advanced Non-Small Cell Lung CancerAdvanced CancerNCT02750514Bristol-Myers Squibb295
终止
2 期
Nivolumab, Ixazomib, Cyclophosphamide, and Dexamethasone in Relapsed/Refractory MyelomaRelapsed Multiple MyelomaRefractory Multiple MyelomaNCT04119336Andrew Yee, MD2