Nivolumab in Association With Radiotherapy and Cisplatin in Locally Advanced Cervical Cancers Followed by Adjuvant Nivolumab for up to 6 Months (NiCOL)

NCT03298893 | Completed Phase 1 DMC

• 1 other identifier: IC 2016-08
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cervical Cancer; Locally Advanced Cervical Cancer

Keywords

cervical cancer; nivolumab; cisplatin; radiotherapy

Outcome Measures

Primary Outcomes (1)

• rate of occurrence of dose-limiting toxicity (DLT)

  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.

  within 11 weeks after the initiation of treatment.

Secondary Outcomes (9)

• 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

• Disease Free Survival (DFS)

  2 years

• 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

• 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

Study Arms (1)

Nivolumab + radiochemotherapy

EXPERIMENTAL

5 weeks of radiochemotherapy + nivolumab followed by 5 months of nivolumab alone

Drug: Nivolumab Injection; Drug: Cisplatin; Radiation: radiotherapy

Interventions

Nivolumab Injection DRUG

2 possible doses : flat dose 240 mg q2 weeks or 1mg/kg q2 weeks

Nivolumab + radiochemotherapy

Cisplatin DRUG

40 mg/m2, once a week during radiotherapy

Nivolumab + radiochemotherapy

radiotherapy RADIATION

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.

Nivolumab + radiochemotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.

You may not qualify if:

• 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;
• Positive serology for hepatitis B surface antigen;
• Positive for hepatitis-C ribonucleic acid on polymerase chain reaction;
• Active infection requiring therapy;

Sponsors & Collaborators

• Institut Curie: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Institut Curie

Paris, 75005, France

Location

Hopital Européen Georges Pompidou

Paris, 75015, France

Location

Institut Curie Hopital René Huguenin

Saint-Cloud, 9220, France

Location

Related Publications (1)

• Rodrigues M, Vanoni G, Loap P, Dubot C, Timperi E, Minsat M, Bazire L, Durdux C, Fourchotte V, Laas E, Pouget N, Castel-Ajgal Z, Marret G, Lesage L, Meseure D, Vincent-Salomon A, Lecompte L, Servant N, Vacher S, Bieche I, Malhaire C, Huchet V, Champion L, Kamal M, Amigorena S, Lantz O, Chevrier M, Romano E. Nivolumab plus chemoradiotherapy in locally-advanced cervical cancer: the NICOL phase 1 trial. Nat Commun. 2023 Jun 22;14(1):3698. doi: 10.1038/s41467-023-39383-8.

  PMID: 37349318 RESULT

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Nivolumab; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Emanuela Romano, MD

  Institut Curie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 2, 2017
• Study Start: November 27, 2017
• Primary Completion: October 30, 2020
• Study Completion: March 7, 2022
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.
• Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).

Locations

FR (3)