Clinical trial NCT05492123: Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer
Official title: Randomized Phase II Study to Evaluate Induction Nivolumab-Ipilimumab, Followed by Nivolumab With Chemoradiotherapy Versus Chemoradiotherapy for Advanced Cervical Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Uterine Cervical Neoplasms
Keywords: Uterine Cervical Neoplasms
Nivolumab
Ipilimumab
Chemoradiation
Anti-PD1
Anti-PDL1
Anti-CTLA4
Immunotherapy
Lead sponsor: Hospital Israelita Albert Einstein
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Brava
First posted: 2022-08-08
Enrollment: 112
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective randomized trial, stratified by center, disease stage and type of radiation
Primary purpose: TREATMENT

Brief summary: A total of 112 patients with locally advanced cervical cancer will be randomized 1:1 to standard therapy with cisplatin-based chemoradiation or nivolumab-ipilimumab induction followed by cisplatin-based chemoradiation. The primary outcome will be 3-year disease-free survival.

Detailed description: Patients with adenocarcinoma or squamous cell carcinoma of the cervix, FIGO Stage IB2-IB3 node positive or Stage IIB-IVA will be randomized to conventional cisplatin-based chemo-radiation or to 4 cycles of induction immunotherapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks, followed by cisplatin chemo-radiation with concurrent nivolumab 240mg every 2 weeks. Primary outcome will be 3-year progression-free survival.

Eligibility criteria: Inclusion Criteria:

* Female participants older than 18 years
* Documented evidence of cervical adenocarcinoma or squamous carcinoma FIGO Stage IB2-IB3 node positive or Stage IIB-IVA
* No prior chemotherapy, immune checkpoint inhibitors or radiotherapy for cervical cancer
* WHO/ECOG performance status of 0-1
* At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion at baseline.

Exclusion Criteria:

* Diagnosis of small cell (neuroendocrine) histology cervical cancer
* Intent to administer a fertility-sparing treatment regimen
* Undergone a previous hysterectomy
* Evidence of metastatic disease per RECIST 1.1 including lymph nodes ≥15 mm (short axis) above the L1 cephalad body or outside the planned radiation field.
* History of allogeneic organ transplantation
* Active or prior documented autoimmune or inflammatory disorders
* Uncontrolled intercurrent illness
* History of another primary malignancy and active primary immunodeficiency
* Patients with active infection

Laboratory values that fall into:

1. WBC count (WBC) \< 2000/μL ;
2. Neutrophil count \< 1500/μL;
3. Platelet count \< 100 x 103/μL;
4. Hemoglobin level \< 9.0 g/dL;
5. Serum creatinine \> 1.5 x upper limit of normal (ULN) unless creatinine clearance is

   ≥ 40 mL/min (measured or calculated using the Cockcroft-Gault formula);
6. Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT): \> 3.0 x ULN;
7. Total bilirubin \> 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of \< 3.0 x ULN);
8. Any positive test result for hepatitis B virus or hepatitis C virus that indicates the presence of the virus, for example, positive Hepatitis B surface antigen (HBsAg, Australia antigen) or Hepatitis C antibodies (anti- HCV) positive (unless the HCV-RNA is negative).

   * Participants with a condition requiring systemic treatment or with corticosteroids (\>10 mg daily of a prednisone equivalent) or other immunosuppressive drugs within 14 days of initiating study treatment.
   * Pregnant or breastfeeding woman

Primary outcomes:
measure: 3-year progression-free survival
timeFrame: 3 years
Secondary outcomes:
measure: 3-year overall survival
timeFrame: 3 years
measure: Objective response rate
timeFrame: 90 days after the end of chemoradiation
measure: Response duration
timeFrame: Through study completion, an average of 3 year
measure: To evaluate health related quality of life (HRQoL): defined as the change from baseline of disease-related symptoms and quality of life of patients undergoing treatment Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer
timeFrame: Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
measure: Evaluate health related quality of life using supplemental cervical cancer module (EORTC CX24) to evaluate patients submitted to treatment with Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer.
timeFrame: Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
measure: Treatment-related toxicity
timeFrame: Through study completion, an average of 3 year
Other outcomes:
Locations:
city: Salvador
country: Brazil
facility: Clinica AMO
state: Bahia
city: Fortaleza
country: Brazil
facility: CRIO -Centro Regional Integrado de Oncologia
state: Ceará
city: Belo Horizonte
country: Brazil
facility: Hospital das Clinicas da UFMG
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Recife
country: Brazil
facility: Multi Oncoclinicas Recife
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas - PUCRS
state: Rio Grande Do Sul
city: Boa Vista
country: Brazil
facility: Universidade Federal de Roraima
state: Roraima
city: Florianópolis
country: Brazil
facility: CEPON - Florianópolis
state: Santa Catarina
city: Barretos
country: Brazil
facility: Hospital de Amor
state: São Paulo
city: São José Do Rio Preto
country: Brazil
facility: Hospital De Base de São José do Rio Preto - CIP São José
state: São Paulo
city: Rio De Janeiro
country: Brazil
facility: INCA - Instituto Nacional do Cancer
city: São Paulo
country: Brazil
facility: AC Camargo Cancer Center
city: São Paulo
country: Brazil
facility: Hospital Municipal Vila Santa Catarina
city: São Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
Study officials:
affiliation: Hospital Israelita Albert Einstein
name: Fernando Maluf, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008 Dec 10;26(35):5802-12. doi: 10.1200/JCO.2008.16.4368. Epub 2008 Nov 10.
citation: Naumann RW, Hollebecque A, Meyer T, Devlin MJ, Oaknin A, Kerger J, Lopez-Picazo JM, Machiels JP, Delord JP, Evans TRJ, Boni V, Calvo E, Topalian SL, Chen T, Soumaoro I, Li B, Gu J, Zwirtes R, Moore KN. Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial. J Clin Oncol. 2019 Nov 1;37(31):2825-2834. doi: 10.1200/JCO.19.00739. Epub 2019 Sep 5.
citation: Santin AD, Deng W, Frumovitz M, Buza N, Bellone S, Huh W, Khleif S, Lankes HA, Ratner ES, O'Cearbhaill RE, Jazaeri AA, Birrer M. Phase II evaluation of nivolumab in the treatment of persistent or recurrent cervical cancer (NCT02257528/NRG-GY002). Gynecol Oncol. 2020 Apr;157(1):161-166. doi: 10.1016/j.ygyno.2019.12.034. Epub 2020 Jan 7.