Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer

Официальное название

Randomized Phase II Study to Evaluate Induction Nivolumab-Ipilimumab, Followed by Nivolumab With Chemoradiotherapy Versus Chemoradiotherapy for Advanced Cervical Cancer

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Nivolumab 40 mg in 4 ml Injection
  Nivolumab 1mg/kg every 3 weeks for 4 cycles prior to radiation and 240mg every 2 weeks with concurrent radiation
• Препарат Ipilimumab 200 MG in 40 ML Injection
  Ipilimumab 3mg/kg every 3 weeks for 4 cycles prior to radiation
• Лучевая терапия Chemoradiation
  Radiation to a dose of 45Gy over 25 1.8Gyfractions and brachytherapy with concurrent weekly cisplatin 40mg/m2/w or carboplatin AUC 2/w

Первичные конечные точки

• 3-year progression-free survival [Срок оценки: 3 years]

Вторичные конечные точки (6)

• 3-year overall survival [Срок оценки: 3 years]
• Objective response rate [Срок оценки: 90 days after the end of chemoradiation]
• Response duration [Срок оценки: Through study completion, an average of 3 year]
• 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 [Срок оценки: Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).]
• 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. [Срок оценки: Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).]
• Treatment-related toxicity [Срок оценки: Through study completion, an average of 3 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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:

• WBC count (WBC) < 2000/μL ;
• Neutrophil count < 1500/μL;
• Platelet count < 100 x 103/μL;
• Hemoglobin level < 9.0 g/dL;
• 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);

• Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT): > 3.0 x ULN;
• Total bilirubin > 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of < 3.0 x ULN);
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бразилия · 14 центров

• CRIO -Centro Regional Integrado de Oncologia — Fortaleza
• Clinica AMO — Salvador
• Hospital das Clinicas da UFMG — Belo Horizonte
• Hospital Erasto Gaertner — Curitiba
• Multi Oncoclinicas Recife — Recife
• Hospital São Lucas - PUCRS — Porto Alegre
• Universidade Federal de Roraima — Boa Vista
• CEPON - Florianópolis — Florianópolis
• … и ещё 6 центров

Публикации

• 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. PMID 19001332
• 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- PMID 31487218
• 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. PMID 31924334

Идентификаторы

NCT: NCT05492123 · BRAVA- Cervical - SGPP 5031-21

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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