Back to resultsNivolumab-ipilimumab and Chemoradiation for Cervical Cancer
Primary Purpose
Uterine Cervical Neoplasms
Status
Recruiting
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Nivolumab 40 mg in 4 ml Injection
Ipilimumab 200 MG in 40 ML Injection
Chemoradiation
Sponsored by
About this trial
This is an interventional treatment trial for Uterine Cervical Neoplasms focused on measuring Uterine Cervical Neoplasms, Nivolumab, Ipilimumab, Chemoradiation, Anti-PD1, Anti-PDL1, Anti-CTLA4, Immunotherapy
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:
- 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
Sites / Locations
- Clinica AMO
- CRIO -Centro Regional Integrado de OncologiaRecruiting
- Hospital das Clinicas da UFMG
- Hospital Erasto Gaertner
- Multi Oncoclinicas RecifeRecruiting
- Hospital São Lucas - PUCRS
- Universidade Federal de RoraimaRecruiting
- CEPON - Florianópolis
- Hospital de Amor
- Hospital De Base de São José do Rio Preto - CIP São José
- INCA - Instituto Nacional do Cancer
- AC Camargo Cancer Center
- Hospital Municipal Vila Santa CatarinaRecruiting
- Hospital Israelita Albert EinsteinRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Standard Chemoradiation
Immunotherapy
Arm Description
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
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.
Outcomes
Primary Outcome Measures
3-year progression-free survival
No evidence of disease recurrence/regrowth after 3 years of follow-up
Secondary Outcome Measures
3-year overall survival
Rate of survival 3 years after the end of chemoradiation
Objective response rate
RECIST response
Response duration
Time from maximum response to disease progression
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
Evaluate health related quality of life using the instrument EORTC QLQ-C30 v3 based on European Organization for Research and Treatment of Cancer (EORTC). The EORTC QLQ-C30 v3 questionnaire, consisting of 30 questions covering 15 domains, divided into three distinct scales: state scale global health and quality of life (it has only one domain, global health measure); functional scale (physical function, role performance, emotional function, cognitive function and social function domains); and symptom scale (fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea and financial difficulties). The scores on each scale range from 0 - 100. The global and functional health scales indicate better quality of life as their score approaches 100. For the symptoms scale, the analysis is inverse, with better performance for quality of life when the scores approach the score minimum (zero).
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.
The EORTC - CX24 questionnaire contains 24 questions, divided into three multiple-item scales and six single-item scales, of which 11 refer to symptoms (questions 31-37, 39 and 41-43), three about body image. (questions 45-47), four questions on sexual/vaginal function (questions 50-53), one on lymphedema (question 38), one for evaluation of peripheral neuropathy (question 40), one for evaluation of menopausal symptoms (question 44) ), one on sexual concerns (question 48), one on sexual activity (question 49) and one on sexual pleasure (question 54). The answers are transformed into a score from 0 - 100 and calculated separately for each scale.
Treatment-related toxicity
Treatment-related toxicity according to CTCAE version 4.0 (Common Toxicity Criteria for Adverse Events )
Full Information
NCT ID
NCT05492123
First Posted
July 22, 2022
Last Updated
December 1, 2022
Sponsor
Hospital Israelita Albert Einstein
Collaborators
Bristol-Myers Squibb, Brava
1. Study Identification
Unique Protocol Identification Number
NCT05492123
Brief Title
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
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 30, 2022 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
March 31, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital Israelita Albert Einstein
Collaborators
Bristol-Myers Squibb, Brava
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uterine Cervical Neoplasms
Keywords
Uterine Cervical Neoplasms, Nivolumab, Ipilimumab, Chemoradiation, Anti-PD1, Anti-PDL1, Anti-CTLA4, Immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Prospective randomized trial, stratified by center, disease stage and type of radiation
Masking
None (Open Label)
Allocation
Randomized
Enrollment
112 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard Chemoradiation
Arm Type
Active Comparator
Arm Description
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
Arm Title
Immunotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Nivolumab 40 mg in 4 ml Injection
Other Intervention Name(s)
Opdivo
Intervention Description
Nivolumab 1mg/kg every 3 weeks for 4 cycles prior to radiation and 240mg every 2 weeks with concurrent radiation
Intervention Type
Drug
Intervention Name(s)
Ipilimumab 200 MG in 40 ML Injection
Other Intervention Name(s)
Yervoy
Intervention Description
Ipilimumab 3mg/kg every 3 weeks for 4 cycles prior to radiation
Intervention Type
Radiation
Intervention Name(s)
Chemoradiation
Other Intervention Name(s)
Cisplatin-based chemoradiation
Intervention Description
Radiation to a dose of 45Gy over 25 1.8Gyfractions and brachytherapy with concurrent weekly cisplatin 40mg/m2/w or carboplatin AUC 2/w
Primary Outcome Measure Information:
Title
3-year progression-free survival
Description
No evidence of disease recurrence/regrowth after 3 years of follow-up
Time Frame
3 years
Secondary Outcome Measure Information:
Title
3-year overall survival
Description
Rate of survival 3 years after the end of chemoradiation
Time Frame
3 years
Title
Objective response rate
Description
RECIST response
Time Frame
90 days after the end of chemoradiation
Title
Response duration
Description
Time from maximum response to disease progression
Time Frame
Through study completion, an average of 3 year
Title
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
Description
Evaluate health related quality of life using the instrument EORTC QLQ-C30 v3 based on European Organization for Research and Treatment of Cancer (EORTC). The EORTC QLQ-C30 v3 questionnaire, consisting of 30 questions covering 15 domains, divided into three distinct scales: state scale global health and quality of life (it has only one domain, global health measure); functional scale (physical function, role performance, emotional function, cognitive function and social function domains); and symptom scale (fatigue, nausea and vomiting, pain, dyspnea, insomnia, loss of appetite, constipation, diarrhea and financial difficulties). The scores on each scale range from 0 - 100. The global and functional health scales indicate better quality of life as their score approaches 100. For the symptoms scale, the analysis is inverse, with better performance for quality of life when the scores approach the score minimum (zero).
Time Frame
Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
Title
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.
Description
The EORTC - CX24 questionnaire contains 24 questions, divided into three multiple-item scales and six single-item scales, of which 11 refer to symptoms (questions 31-37, 39 and 41-43), three about body image. (questions 45-47), four questions on sexual/vaginal function (questions 50-53), one on lymphedema (question 38), one for evaluation of peripheral neuropathy (question 40), one for evaluation of menopausal symptoms (question 44) ), one on sexual concerns (question 48), one on sexual activity (question 49) and one on sexual pleasure (question 54). The answers are transformed into a score from 0 - 100 and calculated separately for each scale.
Time Frame
Baseline (time from screening - before starting treatment) and at the end of treatment (56 days after the last dose of radiotherapy).
Title
Treatment-related toxicity
Description
Treatment-related toxicity according to CTCAE version 4.0 (Common Toxicity Criteria for Adverse Events )
Time Frame
Through study completion, an average of 3 year
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
95 Years
Accepts Healthy Volunteers
No
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:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Diogo Bugano, MD
Phone
+55-11-2151-0240
Email
diogo.gomes@einstein.br
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando Maluf, MD
Organizational Affiliation
Hospital Israelita Albert Einstein
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinica AMO
City
Salvador
State/Province
Bahia
ZIP/Postal Code
41810-011
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aknar Calabrich
Phone
+55(71)3021-8735
Email
aknar@clinicaamo.com.br
First Name & Middle Initial & Last Name & Degree
Aknar Calabrich
Facility Name
CRIO -Centro Regional Integrado de Oncologia
City
Fortaleza
State/Province
Ceará
ZIP/Postal Code
60335-480
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eduardo Cronemberger
Phone
+55(85)3286-5934
Email
cronmeberger.eduardo@gmail.com
First Name & Middle Initial & Last Name & Degree
Eduardo Cronemberger, MD
Facility Name
Hospital das Clinicas da UFMG
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30130-100
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Angélica Nogueira
Phone
+55(31)3307-9255
Email
angélica.onco@uol.com.br
First Name & Middle Initial & Last Name & Degree
Angélica Nogueira, MD
Facility Name
Hospital Erasto Gaertner
City
Curitiba
State/Province
Paraná
ZIP/Postal Code
81520-060
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reitan Ribeiro
Phone
+55(41)3361-5195
Email
reitanribeiro@hotmail.com
First Name & Middle Initial & Last Name & Degree
Reitan Ribeiro, MD
Facility Name
Multi Oncoclinicas Recife
City
Recife
State/Province
Pernambuco
ZIP/Postal Code
50070-460
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carla Rameri
Phone
+55(81)2122-4792
Email
carla.rameri.de.azevedo@gmail.com
First Name & Middle Initial & Last Name & Degree
Carla Rameri, MD
Facility Name
Hospital São Lucas - PUCRS
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90610-001
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernanda Damian
Phone
+55(51)3320-3039
Email
fernandadamian@yahoo.com.br
First Name & Middle Initial & Last Name & Degree
Fernanda Damian
Facility Name
Universidade Federal de Roraima
City
Boa Vista
State/Province
Roraima
ZIP/Postal Code
69310-000
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allex Jardim
Phone
+55(95)3224-4712
Email
allex.j.fonseca@gmail.com
First Name & Middle Initial & Last Name & Degree
Allex Jardim, MD, PhD
Facility Name
CEPON - Florianópolis
City
Florianópolis
State/Province
Santa Catarina
ZIP/Postal Code
88034-000
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne Schmitz
Phone
+55(48)3331-1553
Email
anneschmitz@uol.com.br
First Name & Middle Initial & Last Name & Degree
Anne Schmitz, MD
Facility Name
Hospital de Amor
City
Barretos
State/Province
São Paulo
ZIP/Postal Code
14784-400
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Fernanda Biazzotto
Phone
+55(17)3321-6638
Email
nandabiazotto@hotmail.com
First Name & Middle Initial & Last Name & Degree
Maria Fernanca Biazzotto, MD
Facility Name
Hospital De Base de São José do Rio Preto - CIP São José
City
São José Do Rio Preto
State/Province
São Paulo
ZIP/Postal Code
15090-000
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
João Daniel
Phone
+55(17)3201-5054
Email
joaodcguedes@gmail.com
First Name & Middle Initial & Last Name & Degree
João Daniel, MD
Facility Name
INCA - Instituto Nacional do Cancer
City
Rio De Janeiro
ZIP/Postal Code
20230-130
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adriana Melo
Phone
+55(21)3207-2985
Email
andreia.melo@inca.gov.br
First Name & Middle Initial & Last Name & Degree
Andreia Melo, MD
Facility Name
AC Camargo Cancer Center
City
São Paulo
ZIP/Postal Code
01509-001
Country
Brazil
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natasha Carvalho
Phone
+55(11)2189-5021
Email
natasha.pandolfi@accamargo.org.br
First Name & Middle Initial & Last Name & Degree
Natasha Carvalho, MD
Facility Name
Hospital Municipal Vila Santa Catarina
City
São Paulo
ZIP/Postal Code
04378-500
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana Lucia Neves
Phone
2151-1223
Ext
0
Email
ana.neves@einstein.br
First Name & Middle Initial & Last Name & Degree
Henrique A Helber, MD
Facility Name
Hospital Israelita Albert Einstein
City
São Paulo
ZIP/Postal Code
05652-900
Country
Brazil
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fernando Maluf
First Name & Middle Initial & Last Name & Degree
Diogo Bugano
Email
diogo.gomes@einstein.br
First Name & Middle Initial & Last Name & Degree
Fernando Maluf
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
19001332
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.
Results Reference
background
PubMed Identifier
31487218
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.
Results Reference
background
PubMed Identifier
31924334
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.
Results Reference
background
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Nivolumab-ipilimumab and Chemoradiation for Cervical Cancer
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