Nivolumab in Association With Radiotherapy and Cisplatin in Locally Advanced Cervical Cancers Followed by Adjuvant Nivolumab for up to 6 Months (NiCOL)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03298893|
Recruitment Status : Active, not recruiting
First Posted : October 2, 2017
Last Update Posted : October 6, 2020
|Condition or disease||Intervention/treatment||Phase|
|Cervical Cancer Locally Advanced Cervical Cancer||Drug: Nivolumab Injection Drug: Cisplatin Radiation: radiotherapy||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||November 27, 2017|
|Estimated Primary Completion Date :||October 30, 2020|
|Estimated Study Completion Date :||September 15, 2022|
Experimental: Nivolumab + radiochemotherapy
5 weeks of radiochemotherapy + nivolumab followed by 5 months of nivolumab alone
Drug: Nivolumab Injection
2 possible doses : flat dose 240 mg q2 weeks or 1mg/kg q2 weeks
40 mg/m2, once a week during radiotherapy
Intensity-modulated radiation therapy (including volumetric-modulated arc therapy and tomography) will be used. A dose of 45 Gy will be delivered to the pelvis in 25 fractions of 1.8 Gy using a 6-MV photon energy.
An additional dose of 54 Gy in 25 fractions of 2.16 Gy may be delivered to invaded lymph nodes using SIB-IMRT.
An additional lateral pelvic dose may be delivered if coverage of the target volumes is judged insufficient. The volumes, doses and techniques will be those usually used in each center.
- rate of occurrence of dose-limiting toxicity (DLT) [ Time Frame: 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.
- Objective Response Rate (ORR) [ Time Frame: after the end of RT and before brachytherapy and again up to 2 months after brachytherapy ]ORR is defined as the proportion of all subjects whose best response is either a complete response or a partial response.
- Progression Free Survival (PFS) [ Time Frame: 2 years ]PFS is defined as the length of time from the start of treatment to disease progression or death, regardless of the cause of death
- Disease Free Survival (DFS) [ Time Frame: 2 years ]DFS is defined as the length of time from the start of complete response to the time of relapse from complete response. DFS applies only to patients in complete response.
- Incidence of Serious Adverse Events (SAEs) to assess the overall safety profile of the association of nivolumab and pelvic radio-chemotherapy [ Time Frame: from the first intake of the IMP until 100 days after the last intake of the IMP ]
- Incidence of Adverse Events (AEs) to assess the overall safety profile of the association of nivolumab and pelvic radio-chemotherapy [ Time Frame: from the first intake of the IMP until 100 days after the last intake of the IMP ]
- validation of molecular alterations detected by molecular analyses [ Time Frame: 2 years ]Retrospective exome, RNA and targeted sequencing analyses will be performed on all patients treated and for whom tumor samples are available.
- ctDNA heterogeneity [ Time Frame: baseline, at Weeks 3, 6 and 12 and every 12 weeks up to Week 104 ]Retrospective exome and targeted sequencing analyses will be performed on all patients treated and for whom tissue samples are available at the different timepoints
- tumor microenvironment description [ Time Frame: 2 years ]phenotypic analysis of the different components of the tumor microenvironment using various technologies
- tumor PD-L1 immunohistochemistry [ Time Frame: 2 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298893
|Paris, France, 75005|
|Hopital Européen Georges Pompidou|
|Paris, France, 75015|
|Institut Curie Hopital René Huguenin|
|Saint Cloud, France, 9220|
|Study Director:||Emanuela Romano, MD||Institut Curie|