Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer (AddChemo)

July 28, 2024 updated by: Hospital do Coracao

Adjuvant Chemotherapy in Cell-free Human Papillomavirus Deoxyribonucleic Acid (cfHPV-DNA) Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer (CC)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

365

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
    • AM
      • Manaus, AM, Brazil, 69.020-030
        • Recruiting
        • Centro Integrado de Pesquisa da Amazônia, CINPAM
        • Contact:
        • Principal Investigator:
          • Gilmara Resende
    • BA
      • Vitória Da Conquista, BA, Brazil, 45.023-145
        • Not yet recruiting
        • Hospital Samur
        • Contact:
        • Principal Investigator:
          • Augusto Madureira
    • DF
      • Brasília, DF, Brazil, 70.335-900
        • Not yet recruiting
        • Hospital de Base do Distrito Federal
        • Contact:
        • Principal Investigator:
          • Luiza Weis
    • ES
      • Cachoeiro De Itapemirim, ES, Brazil, 29.308-065
        • Not yet recruiting
        • Hospital Evangélico de Cachoeiro de Itapemirim
        • Contact:
        • Principal Investigator:
          • Sabina Aleixo
    • MG
      • Muriaé, MG, Brazil, 36.888-233
        • Recruiting
        • Hospital do Câncer de Muriaé
        • Contact:
        • Principal Investigator:
          • Paula Gonçalves
    • PR
      • Cascavel, PR, Brazil, 85.803-760
        • Not yet recruiting
        • Centro de Oncologia de Cascavel, CEONC
        • Contact:
        • Principal Investigator:
          • Jordana Resende
      • Cascavel, PR, Brazil, 85.810-031
        • Not yet recruiting
        • União Oeste Paranaense de Estudos e Combate ao Câncer, UOPECCAN
        • Contact:
        • Principal Investigator:
          • Aline Gongora
      • Curitiba, PR, Brazil, 80810-050
        • Not yet recruiting
        • Centro Integrado de Oncologia de Curitiba, CIONC
        • Contact:
        • Principal Investigator:
          • Karina Vianna
    • RJ
      • Rio de Janeiro, RJ, Brazil, 20.220-410
        • Recruiting
        • Instituto Nacional do Câncer, INCA
        • Contact:
          • Andreia Melo
          • Phone Number: (21) 3207-1000
        • Contact:
    • RN
      • Natal, RN, Brazil, 59.062-000
        • Not yet recruiting
        • Liga Norte Riograndense Contra O Cancer
        • Principal Investigator:
          • Sulene Oliveira
        • Contact:
    • RR
      • Boa Vista, RR, Brazil, 69.304-015
        • Not yet recruiting
        • Centro Oncologico de Roraima, CECOR
        • Principal Investigator:
          • Allex Fonseca
        • Contact:
    • RS
      • Bento Gonçalves, RS, Brazil, 95.700-084
        • Not yet recruiting
        • Hospital Tacchini
        • Contact:
        • Principal Investigator:
          • Alessandra Kaercher
      • Caxias Do Sul, RS, Brazil, 95.070-561
        • Not yet recruiting
        • Hospital Geral de Caxias do Sul
        • Contact:
        • Principal Investigator:
          • Janaina Brollo
      • Lajeado, RS, Brazil, 95.900-010
        • Not yet recruiting
        • Hospital Bruno Born
        • Contact:
        • Principal Investigator:
          • Rafael Seewald
      • Porto Alegre, RS, Brazil, 90.850- 170
        • Not yet recruiting
        • Centro Gaúcho Integrado Hospital Mãe de Deus
        • Contact:
        • Principal Investigator:
          • Christina Kussler
    • SC
      • Itajaí, SC, Brazil, 88.301-220
        • Not yet recruiting
        • Catarina Pesquisa Clinica
        • Principal Investigator:
          • Giuliano Borges
        • Contact:
      • Joinville, SC, Brazil, 89.204-061
    • SP
      • Campinas, SP, Brazil, 13.083-881
        • Not yet recruiting
        • Centro de Atenção Integral a Saúde da Mulher, CAISM
        • Contact:
        • Principal Investigator:
          • Diama Vale
      • Jales, SP, Brazil, 15.706-396
        • Not yet recruiting
        • Hospital do Amor
        • Contact:
        • Principal Investigator:
          • Túlio Furquim
      • Sao Paulo, SP, Brazil, 04.005-000
        • Recruiting
        • Hospital do Coração - Research Institute
        • Principal Investigator:
          • Michelle S Almeida, PhD
        • Contact:
      • São Paulo, SP, Brazil, 01.206-001
        • Recruiting
        • Hospital da Mulher - SECONCI
        • Contact:
        • Principal Investigator:
          • Marcela Bonalumi
      • São Paulo, SP, Brazil, 04.015-070
        • Not yet recruiting
        • Instituto Brasileiro de Combate ao Câncer, IBCC São Camilo
        • Contact:
        • Principal Investigator:
          • Renata Meneguetti
      • São Paulo, SP, Brazil, 04.024-002
        • Not yet recruiting
        • Hospital São Paulo, Unifesp
        • Contact:
        • Principal Investigator:
          • Hakaru Tadokoro
        • Sub-Investigator:
          • Vinicius Agibert
      • São Paulo, SP, Brazil, 08.270-120
        • Recruiting
        • Hospital Santa Marcelina
        • Contact:
        • Principal Investigator:
          • Thais Almeida
      • São Paulo, SP, Brazil, 09.060-650
        • Not yet recruiting
        • Centro de Estudos e Pesquisa de Hematologia, CEPHO
        • Principal Investigator:
          • Patricia Santi
        • Contact:
      • Taubate, SP, Brazil, 12.030-200

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Control Arm (Standard of Care)
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.
Other: Follow-up
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.
Experimental: Experimental Arm
Receive two cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days. After that, 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.
Drug: cisplatin, gemcitabine
Two additional cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days.
Other: Follow-up
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: 120 days
Progression-free survival will be calculated from the date of randomization until the date of progression, whether local or distant, or death.
120 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 120 days
Pverall survival will be calculated from the date of randomization until death or last follow-up. Follow-up will be updated at each consultation and the following possibilities will be considered: living without disease, living with disease, death from cancer, death from another cause and loss of follow-up.
120 days
Overall response rate
Time Frame: 120 days
Response assessment will be performed using RECIST 1.1 (2009) criteria through pelvic MRI. Thus, complete response (CR) will be considered the disappearance of all lesions. Partial response (PR), reduction (30%) in the sum of the largest diameters of target lesions, when compared to the initial examination. Disease progression (PD): increase (20%) in the sum of the largest diameters of the lesions, when compared to the initial examination or the appearance of new lesions. Stable disease: does not meet criteria for PR or PD.
120 days
Quality of life measures (EORTC QLQ-C30 and QLC-CX24)
Time Frame: 21 to 120 days
Generic quality of life measures (EORTC QLQ-C30) will be assessed during medical consultations in this clinical study, considering that this questionnaire alone does not adequately assess specific treatment issues that affect the quality of life of women with cervical cancer, a QLQ-CX24 add-on module will also be applied. All questionnaires used in this study are self-administered, however, in those cases where the ability to understand, little education/illiteracy is considered low or when telephone monitoring is in force, the tests will be applied by the researchers, who will seek to read all the questions and help mark answers.
21 to 120 days
Toxicity according to the Common Terminology Criteria for Adverse Events v.5.0
Time Frame: 7 to 120 days
Toxicity will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (2017). Hematological (anemia, neutropenia, thrombocytopenia and febrile neutropenia), gastrointestinal (diarrhea, nausea and vomiting), renal (serum creatinine changes) and hepatic (AST and ALT changes) toxicities will be evaluated. Grade 1 and 2 toxicities, together, were considered mild and grade 3 and 4 toxicities were considered severe.
7 to 120 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital do Coracao

Collaborators

University of Sao Paulo

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 27, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

March 1, 2023

First Submitted That Met QC Criteria

March 1, 2023

First Posted (Actual)

March 10, 2023

Study Record Updates

Last Update Posted (Actual)

July 30, 2024

Last Update Submitted That Met QC Criteria

July 28, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AddChemo CC Trial

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data could be shared after reasonable request of the principal investigator.

IPD Sharing Time Frame

After study completion.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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