Trial Title:
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer
NCT ID:
NCT05764044
Condition:
Cervical Cancer
Cervix Cancer
Cervix Neoplasm
Conditions: Official terms:
Uterine Cervical Neoplasms
Gemcitabine
Conditions: Keywords:
Human papillomavirus
HPV
Cervical cancer
Circulating free DNA
Adjuvant chemotherapy
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
A prospective, randomized, multicenter, national, superiority, parallel, clinical trial,
design to evaluate the use of adjuvant chemotherapy in patients with locally advanced
cervical cancer, selected by cfDNA-HPV biomarker. Intervention arm will count on
application of two additional cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1
and gemcitabine 1000mg/m2 D1 and D8 at every 21 days. Randomization will be allocated
1:1. Participants will be followed at every 4 months, in person or by phone. Primary
endpoint is progression-free survival time.
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
cisplatin, gemcitabine
Description:
Two additional cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine
1000mg/m2 D1 and D8 at every 21 days.
Arm group label:
Experimental Arm
Intervention type:
Other
Intervention name:
Follow-up
Description:
Patients will be followed with plasma cfDNA-HPV, computed tomography (CT) scan of the
thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological
examination at every four months.
Arm group label:
Control Arm (Standard of Care)
Arm group label:
Experimental Arm
Summary:
This study hypothesizes that patients who persist with cell-free human papillomavirus
deoxyribonucleic acid (cfHPV-DNA) plasma expression at the end of standard treatment, can
derive the benefit of using adjuvant chemotherapy in locally advanced cervical cancer
(CC). After standard treatment based on concomitant chemoradiotherapy regime, a
qualitative and quantitative research of cfHPV-DNA in plasma of patients will be
conducted. Patients who have positive research for plasma cfHPV-DNA at the end of
chemoradiotherapy treatment will be randomized to receive two additional cycles of
adjuvant chemotherapy or observation. Patients will be followed with conduction of
computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and
pelvis and clinical and gynecological examination at every four months.
Detailed description:
A prospective, randomized, multicenter, national, superiority, parallel, clinical trial,
design to evaluate the use of adjuvant chemotherapy in patients with locally advanced
cervical cancer selected by cfDNA-HPV biomarker. Patients will be randomized by
stratified randomization process to belong to one of the groups: control (Group B) or
intervention (Group C), emphasizing homogeneity of risk factors between them. A
randomized list will be generated by using a suitable software, using variable size
blocks (2 or 4), with stratification for site and staging. The confidentiality of the
randomization list will be maintained through an automated, centralized, Internet-based
randomization system, available 24 hours a day (RedCap). Selected patients must receive
standard treatment based on concomitant chemoradiotherapy regime, with dose of radiation
of 40-50 greys (Gy) (considering additional boost of 10-15 Gy in lymph nodes,
radiologically or surgically, compromised) and brachytherapy of 30-40 Gy and cisplatin
40mg/m2 weekly. After four weeks of the end of treatment, a qualitative and quantitative
research of cfHPV-DNA in plasma of patients will be conducted. Those with a negative
qualitative research result will leave the study. Patients who have positive research for
plasma 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, 82
cfHPV-DNA at the end of chemoradiotherapy treatment will be randomized to receive two
additional cycles of adjuvant chemotherapy or observation. In those cases in which the
duration of radiochemotherapy treatment exceeds 84 days, patients must undergo imaging
examination (chest, abdomen and pelvis CT) in order to exclude pre-randomization
metastatic disease. Patients will be followed with conduction of computed tomography (CT)
scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and
gynecological examination at every four months.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3 to IVA
will be included prospectively.
- Previous standard treatment based on concomitant chemoradiotherapy regimen.
- Karnofsky performance status score ≥70, with estimated life expectancy ≥12 weeks,
- Immunocompetent,
- Positive research for types 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59,
66, 68, 69, 73, 82 cfHPV-DNA in plasma at the end of chemoradiotherapy,
- Proper hematological, liver and kidney functions. Inclusion criteria will include
absolute neutrophils count ≥1.5 x 109/L, platelets ≥100 x 10/L, serum bilirubin ≤
2.0 x upper limit of normal (ULN), calculated creatinine clearance ≥50 mL/min and
alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline
phosphatase ≤ 2.5 x ULN.
- Patients of child-bearing potential were obligated to use an approved contraceptive
method during and for 3 months after the study;
- Agree with research procedures, by signing the Informed Consent Form (ICF).
Exclusion Criteria:
- Previous cervical cancer or other malignancies,
- Pregnant women,
- Inability to perform concurrent cisplatin based-chemoradiotherapy.
- Tumors containing different HPV genotypes
- Absence of anatomopathological examination to prove the diagnosis and/or staging
examinations.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Centro Integrado de Pesquisa da Amazônia, CINPAM
Address:
City:
Manaus
Zip:
69.020-030
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Patricia Serra
Phone:
(92) 9130-8097
Email:
coordenacao@cinpam.com.br
Investigator:
Last name:
Gilmara Resende
Email:
Principal Investigator
Facility:
Name:
Hospital Samur
Address:
City:
Vitória Da Conquista
Zip:
45.023-145
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Reinan Ferreira Jr.
Phone:
(77) 2102-8399
Email:
pesquisa@hospitalsamur.com.br
Investigator:
Last name:
Augusto Madureira
Email:
Principal Investigator
Facility:
Name:
Hospital de Base do Distrito Federal
Address:
City:
Brasília
Zip:
70.335-900
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Laryssa Silva
Phone:
(61) 3550-8837
Email:
laryssa.silva@igesdf.org.br
Investigator:
Last name:
Luiza Weis
Email:
Principal Investigator
Facility:
Name:
Hospital Evangélico de Cachoeiro de Itapemirim
Address:
City:
Cachoeiro De Itapemirim
Zip:
29.308-065
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Narelle Parmanhani
Phone:
(28) 3522-5095
Email:
narelle@iosc.com.br
Investigator:
Last name:
Sabina Aleixo
Email:
Principal Investigator
Facility:
Name:
Hospital do Câncer de Muriaé
Address:
City:
Muriaé
Zip:
36.888-233
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Sergio Silva
Phone:
(22) 99928-5576
Email:
sergio.silva@fcv.org.br
Investigator:
Last name:
Paula Gonçalves
Email:
Principal Investigator
Facility:
Name:
Centro de Oncologia de Cascavel, CEONC
Address:
City:
Cascavel
Zip:
85.803-760
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Rosangela Francener
Phone:
(45) 99915-9622
Email:
enfcentrodepesquisa@ceonc.com.br
Investigator:
Last name:
Jordana Resende
Email:
Principal Investigator
Facility:
Name:
União Oeste Paranaense de Estudos e Combate ao Câncer, UOPECCAN
Address:
City:
Cascavel
Zip:
85.810-031
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Taciane Leal
Phone:
(45) 2101-7000
Email:
taciane.leal@uopeccan.org.br
Investigator:
Last name:
Aline Gongora
Email:
Principal Investigator
Facility:
Name:
Centro Integrado de Oncologia de Curitiba, CIONC
Address:
City:
Curitiba
Zip:
80810-050
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Karina Vianna
Phone:
(41) 3024-2421
Email:
pesquisaclinica@cionc.com.br
Investigator:
Last name:
Karina Vianna
Email:
Principal Investigator
Facility:
Name:
Instituto Nacional do Câncer, INCA
Address:
City:
Rio de Janeiro
Zip:
20.220-410
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Andreia Melo
Phone:
(21) 3207-1000
Contact backup:
Last name:
Flavia Alves
Email:
falves@inca.gov.br
Facility:
Name:
Liga Norte Riograndense Contra o Câncer
Address:
City:
Natal
Zip:
59.062-000
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Kleyton Medeiros
Phone:
(84) 99902-6430
Email:
kleyton.medeiros@liga.org.br
Investigator:
Last name:
Sulene Oliveira
Email:
Principal Investigator
Facility:
Name:
Centro Oncologico de Roraima, CECOR
Address:
City:
Boa Vista
Zip:
69.304-015
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Luana Vasconcelos
Phone:
(95) 99118-2722
Email:
luana.luana.silva53@hotmail.com
Investigator:
Last name:
Allex Fonseca
Email:
Principal Investigator
Facility:
Name:
Hospital Tacchini
Address:
City:
Bento Gonçalves
Zip:
95.700-084
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Brenda Santos
Phone:
(54) 3455-4333
Email:
brenda.santos@tacchini.com.br
Investigator:
Last name:
Alessandra Kaercher
Email:
Principal Investigator
Facility:
Name:
Hospital Geral de Caxias do Sul
Address:
City:
Caxias Do Sul
Zip:
95.070-561
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Ramone Bertussi
Phone:
(54) 3218-7328
Email:
rabertus@ucs.br
Investigator:
Last name:
Janaina Brollo
Email:
Principal Investigator
Facility:
Name:
Hospital Bruno Born
Address:
City:
Lajeado
Zip:
95.900-010
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Rafael Seewald
Phone:
(51) 37147558
Email:
pesquisaclinica@hbb.com.br
Investigator:
Last name:
Rafael Seewald
Email:
Principal Investigator
Facility:
Name:
Centro Gaúcho Integrado Hospital Mãe de Deus
Address:
City:
Porto Alegre
Zip:
90.850- 170
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Luis Castro
Phone:
(51) 3307-2943
Email:
luiscastro.pesquisa@gmail.com
Investigator:
Last name:
Christina Kussler
Email:
Principal Investigator
Facility:
Name:
Catarina Pesquisa Clínica
Address:
City:
Itajaí
Zip:
88.301-220
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Julia Bizatto
Phone:
(47) 98432-0028
Email:
julia@catarinapesquisa.com.br
Investigator:
Last name:
Giuliano Borges
Email:
Principal Investigator
Facility:
Name:
Hospital Unimed
Address:
City:
Joinville
Zip:
89.204-061
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Ruthy Fernandes
Phone:
(47)3441-4048
Email:
ruthyf@joinville.unimedsc.com.br
Investigator:
Last name:
Andrea Santin
Email:
Principal Investigator
Facility:
Name:
Centro de Atenção Integral a Saúde da Mulher, CAISM
Address:
City:
Campinas
Zip:
13.083-881
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Regina Barros
Phone:
(19) 3521-9476
Email:
pesquisaonco@caism.unicamp.br
Investigator:
Last name:
Diama Vale
Email:
Principal Investigator
Facility:
Name:
Hospital do Amor
Address:
City:
Jales
Zip:
15.706-396
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Joyce Almeida
Phone:
(17) 3624-3900
Email:
joyce.ramos@hospitaldeamor.com.br
Investigator:
Last name:
Túlio Furquim
Email:
Principal Investigator
Facility:
Name:
Hospital do Coração - Research Institute
Address:
City:
Sao Paulo
Zip:
04.005-000
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Michelle S Almeida, PhD
Phone:
(11) 999112805
Email:
malmeida@hcor.com.br
Investigator:
Last name:
Michelle S Almeida, PhD
Email:
Principal Investigator
Facility:
Name:
Hospital da Mulher - SECONCI
Address:
City:
São Paulo
Zip:
01.206-001
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Jackeline Garcia
Phone:
(11) 99745-3996
Email:
gabriela.dona@unifesp.br
Investigator:
Last name:
Marcela Bonalumi
Email:
Principal Investigator
Facility:
Name:
Instituto Brasileiro de Combate ao Câncer, IBCC São Camilo
Address:
City:
São Paulo
Zip:
04.015-070
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Alayne Yamada
Phone:
(11) 4450-0347
Email:
alayne.yamada@hospitalsaocamilosp.org.br
Investigator:
Last name:
Renata Meneguetti
Email:
Principal Investigator
Facility:
Name:
Hospital São Paulo, Unifesp
Address:
City:
São Paulo
Zip:
04.024-002
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Vinicius Agibert
Email:
v.agibert09@gmail.com
Investigator:
Last name:
Hakaru Tadokoro
Email:
Principal Investigator
Investigator:
Last name:
Vinicius Agibert
Email:
Sub-Investigator
Facility:
Name:
Hospital Santa Marcelina
Address:
City:
São Paulo
Zip:
08.270-120
Country:
Brazil
Status:
Recruiting
Contact:
Last name:
Camila Guedes
Phone:
(11) 2217-3766
Email:
camilacpc@santamarcelina.org
Investigator:
Last name:
Thais Almeida
Email:
Principal Investigator
Facility:
Name:
Centro de Estudos e Pesquisa de Hematologia, CEPHO
Address:
City:
São Paulo
Zip:
09.060-650
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Emanuelle Greque
Phone:
(11) 97402-9832
Email:
emanuelle.greque@cepho.org.br
Investigator:
Last name:
Patricia Santi
Email:
Principal Investigator
Facility:
Name:
Instituo de Câncer Brasil, ICB
Address:
City:
Taubate
Zip:
12.030-200
Country:
Brazil
Status:
Not yet recruiting
Contact:
Last name:
Bruna Campitelli
Phone:
(12) 99212-7022
Email:
brunagiovaneti@institutodocancerbrasil.com.br
Investigator:
Last name:
Luis Zucca
Email:
Principal Investigator
Start date:
March 27, 2024
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Hospital do Coracao
Agency class:
Other
Collaborator:
Agency:
University of Sao Paulo
Agency class:
Other
Source:
Hospital do Coracao
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05764044
