Clinical trial NCT05764044: Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer
Official title: Adjuvant Chemotherapy in Cell-free Human Papillomavirus Deoxyribonucleic Acid (cfHPV-DNA) Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer (CC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cervical Cancer
Cervix Cancer
Cervix Neoplasm
Keywords: Human papillomavirus
HPV
Cervical cancer
Circulating free DNA
Adjuvant chemotherapy
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
Collaborators: name: University of Sao Paulo
First posted: 2023-03-10
Enrollment: 365
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

Brief 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.

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.

Primary outcomes:
measure: Progression free survival
timeFrame: 120 days
Secondary outcomes:
measure: Overall survival
timeFrame: 120 days
measure: Overall response rate
timeFrame: 120 days
measure: Quality of life measures (EORTC QLQ-C30 and QLC-CX24)
timeFrame: 21 to 120 days
measure: Toxicity according to the Common Terminology Criteria for Adverse Events v.5.0
timeFrame: 7 to 120 days
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Centro Integrado de Pesquisa da Amazônia, CINPAM
state: AM
city: Vitória Da Conquista
country: Brazil
facility: Hospital Samur
state: BA
city: Brasília
country: Brazil
facility: Hospital de Base do Distrito Federal
state: DF
city: Cachoeiro De Itapemirim
country: Brazil
facility: Hospital Evangélico de Cachoeiro de Itapemirim
state: ES
city: Muriaé
country: Brazil
facility: Hospital do Câncer de Muriaé
state: MG
city: Cascavel
country: Brazil
facility: Centro de Oncologia de Cascavel, CEONC
state: PR
city: Cascavel
country: Brazil
facility: União Oeste Paranaense de Estudos e Combate ao Câncer, UOPECCAN
state: PR
city: Curitiba
country: Brazil
facility: Centro Integrado de Oncologia de Curitiba, CIONC
state: PR
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional do Câncer, INCA
state: RJ
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer
state: RN
city: Boa Vista
country: Brazil
facility: Centro Oncologico de Roraima, CECOR
state: RR
city: Bento Gonçalves
country: Brazil
facility: Hospital Tacchini
state: RS
city: Caxias Do Sul
country: Brazil
facility: Hospital Geral de Caxias do Sul
state: RS
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
state: RS
city: Porto Alegre
country: Brazil
facility: Centro Gaúcho Integrado Hospital Mãe de Deus
state: RS
city: Itajaí
country: Brazil
facility: Catarina Pesquisa Clínica
state: SC
city: Joinville
country: Brazil
facility: Hospital Unimed
state: SC
city: Campinas
country: Brazil
facility: Centro de Atenção Integral a Saúde da Mulher, CAISM
state: SP
city: Jales
country: Brazil
facility: Hospital do Amor
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital do Coração - Research Institute
state: SP
city: São Paulo
country: Brazil
facility: Hospital da Mulher - SECONCI
state: SP
city: São Paulo
country: Brazil
facility: Instituto Brasileiro de Combate ao Câncer, IBCC São Camilo
state: SP
city: São Paulo
country: Brazil
facility: Hospital São Paulo, Unifesp
state: SP
city: São Paulo
country: Brazil
facility: Hospital Santa Marcelina
state: SP
city: São Paulo
country: Brazil
facility: Centro de Estudos e Pesquisa de Hematologia, CEPHO
state: SP
city: Taubate
country: Brazil
facility: Instituo de Câncer Brasil, ICB
state: SP
Study officials:
References: