- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03298893
Nivolumab in Association With Radiotherapy and Cisplatin in Locally Advanced Cervical Cancers Followed by Adjuvant Nivolumab for up to 6 Months (NiCOL)
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
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Paris, France, 75015
- Hopital Europeen Georges Pompidou
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Paris, France, 75005
- Institut Curie
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Saint Cloud, France, 9220
- Institut Curie Hopital Rene Huguenin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Nivolumab + radiochemotherapy
5 weeks of radiochemotherapy + nivolumab followed by 5 months of nivolumab alone
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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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
rate of occurrence of dose-limiting toxicity (DLT)
Time Frame: within 11 weeks after the initiation of treatment.
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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:
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within 11 weeks after the initiation of treatment.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: after the end of RT and before brachytherapy and again up to 2 months after brachytherapy
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ORR is defined as the proportion of all subjects whose best response is either a complete response or a partial response.
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after the end of RT and before brachytherapy and again up to 2 months after brachytherapy
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Progression Free Survival (PFS)
Time Frame: 2 years
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PFS is defined as the length of time from the start of treatment to disease progression or death, regardless of the cause of death
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2 years
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Disease Free Survival (DFS)
Time Frame: 2 years
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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.
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2 years
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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
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from the first intake of the IMP until 100 days after the last intake of the IMP
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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
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from the first intake of the IMP until 100 days after the last intake of the IMP
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validation of molecular alterations detected by molecular analyses
Time Frame: 2 years
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Retrospective exome, RNA and targeted sequencing analyses will be performed on all patients treated and for whom tumor samples are available.
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2 years
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ctDNA heterogeneity
Time Frame: baseline, at Weeks 3, 6 and 12 and every 12 weeks up to Week 104
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Retrospective exome and targeted sequencing analyses will be performed on all patients treated and for whom tissue samples are available at the different timepoints
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baseline, at Weeks 3, 6 and 12 and every 12 weeks up to Week 104
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tumor microenvironment description
Time Frame: 2 years
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phenotypic analysis of the different components of the tumor microenvironment using various technologies
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2 years
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tumor PD-L1 immunohistochemistry
Time Frame: 2 years
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2 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Emanuela Romano, MD, Institut Curie
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Uterine Neoplasms
- Genital Neoplasms, Female
- Uterine Cervical Diseases
- Uterine Diseases
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Uterine Cervical Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Nivolumab
Other Study ID Numbers
- IC 2016-08
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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