Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer

NCT ID: NCT05492123

Last Updated: 2024-01-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-08-30

Study Completion Date

2028-03-31

Brief Summary

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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

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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.

Conditions

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Uterine Cervical Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective randomized trial, stratified by center, disease stage and type of radiation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard Chemoradiation

Traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week or carboplatin AUC 2/week

Group Type ACTIVE_COMPARATOR

Chemoradiation

Intervention Type RADIATION

Radiation to a dose of 45Gy over 25 1.8Gyfractions and brachytherapy with concurrent weekly cisplatin 40mg/m2/w or carboplatin AUC 2/w

Immunotherapy

4 cycles of induction therapy with nivolumab 1mg/kg and ipilimumab 3mg/kg every 3 weeks followed by traditional radiation therapy with a target of 45 Gy in 25 1.8Gy fractions with concurrent weekly cisplatin 40mg/m2/week (or carboplatin AUC 2/week) with concurrent nivolumab 240mg every 2 weeks.

Group Type EXPERIMENTAL

Nivolumab 40 mg in 4 ml Injection

Intervention Type DRUG

Nivolumab 1mg/kg every 3 weeks for 4 cycles prior to radiation and 240mg every 2 weeks with concurrent radiation

Ipilimumab 200 MG in 40 ML Injection

Intervention Type DRUG

Ipilimumab 3mg/kg every 3 weeks for 4 cycles prior to radiation

Chemoradiation

Intervention Type RADIATION

Radiation to a dose of 45Gy over 25 1.8Gyfractions and brachytherapy with concurrent weekly cisplatin 40mg/m2/w or carboplatin AUC 2/w

Interventions

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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

Intervention Type DRUG

Ipilimumab 200 MG in 40 ML Injection

Ipilimumab 3mg/kg every 3 weeks for 4 cycles prior to radiation

Intervention Type DRUG

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

Intervention Type RADIATION

Other Intervention Names

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Opdivo Yervoy Cisplatin-based chemoradiation

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

95 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

Brava

INDUSTRY

Sponsor Role collaborator

Hospital Israelita Albert Einstein

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fernando Maluf, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Israelita Albert Einstein

Locations

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CRIO -Centro Regional Integrado de Oncologia

Fortaleza, Ceará, Brazil

Site Status RECRUITING

Clinica AMO

Salvador, Estado de Bahia, Brazil

Site Status RECRUITING

Hospital das Clinicas da UFMG

Belo Horizonte, Minas Gerais, Brazil

Site Status NOT_YET_RECRUITING

Hospital Erasto Gaertner

Curitiba, Paraná, Brazil

Site Status NOT_YET_RECRUITING

Multi Oncoclinicas Recife

Recife, Pernambuco, Brazil

Site Status RECRUITING

Hospital São Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status NOT_YET_RECRUITING

Universidade Federal de Roraima

Boa Vista, Roraima, Brazil

Site Status RECRUITING

CEPON - Florianópolis

Florianópolis, Santa Catarina, Brazil

Site Status NOT_YET_RECRUITING

Hospital de Amor

Barretos, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

Hospital De Base de São José do Rio Preto - CIP São José

São José do Rio Preto, São Paulo, Brazil

Site Status NOT_YET_RECRUITING

INCA - Instituto Nacional do Cancer

Rio de Janeiro, , Brazil

Site Status NOT_YET_RECRUITING

AC Camargo Cancer Center

São Paulo, , Brazil

Site Status NOT_YET_RECRUITING

Hospital Municipal Vila Santa Catarina

São Paulo, , Brazil

Site Status RECRUITING

Hospital Israelita Albert Einstein

São Paulo, , Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Diogo Bugano, MD

Role: CONTACT

+55-11-2151-0240

Facility Contacts

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Eduardo Cronemberger

Role: primary

+55(85)3286-5934

Aknar Calabrich

Role: primary

+55(71)3021-8735

Angélica Nogueira

Role: primary

+55(31)3307-9255

Reitan Ribeiro

Role: primary

+55(41)3361-5195

Carla Rameri

Role: primary

+55(81)2122-4792

Fernanda Damian

Role: primary

+55(51)3320-3039

Allex Jardim

Role: primary

+55(95)3224-4712

Anne Schmitz

Role: primary

+55(48)3331-1553

Maria Fernanda Biazzotto

Role: primary

+55(17)3321-6638

João Daniel

Role: primary

+55(17)3201-5054

Adriana Melo

Role: primary

+55(21)3207-2985

Natasha Carvalho

Role: primary

+55(11)2189-5021

Ana Lucia Neves

Role: primary

2151-1223 ext. 0

Fernando Maluf

Role: primary

Diogo Bugano

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 19001332 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31487218 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31924334 (View on PubMed)

Other Identifiers

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BRAVA- Cervical - SGPP 5031-21

Identifier Type: -

Identifier Source: org_study_id

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