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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
365

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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 Evangelico 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 Câncer
        • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospital do Coracao

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 27, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 1, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 10, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 30, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 28, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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