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

Primary Purpose

Cervical Cancer, Cervix Cancer, Cervix Neoplasm

Status
Not yet recruiting
Phase
Phase 3
Locations
Brazil
Study Type
Interventional
Intervention
cisplatin, gemcitabine
Follow-up
Sponsored by
Hospital do Coracao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring Human papillomavirus, HPV, Cervical cancer, Circulating free DNA, Adjuvant chemotherapy

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3 to IVA will be included prospectively. Karnofsky performance status score ≥70, with estimated life expectancy ≥12 weeks, Immunocompetent, Positive research for types 16 or 18 cfHPV-DNA in plasma at diagnosis, Proper hematological, liver and kidney functions. Inclusion criteria will include absolute neutrophils count ≥1.5 x 109/L, platelets ≥100 x 10/L, hemoglobin ≥10,0 g/dL, serum bilirubin ≤ 2.0 x upper limit of normal (ULN), calculated creatinine clearance ≥60 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, Previous HPV vaccination with bivalent or superior vaccine, Period between start and end of chemoradiotherapy treatment superior to eight weeks, Inability to perform concurrent cisplatin based-chemoradiotherapy. Tumors containing different HPV genotypes of 16 or 18.

Sites / Locations

  • Hospital do Coração - Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Control Arm (Standard of Care)

Experimental Arm

Arm Description

Patients will be followed with computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.

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 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.

Outcomes

Primary Outcome Measures

Activation speed
Accessing regulatory process, hiring and training of investigator sites.
Eligibility profile for study of patients with cervical cancer
Analyzing the impact of pandemic on disease diagnosis period.
Potential for recruitment
Potential for recruiting 4 to 12 patients/month in each investigator site is sufficient to reach sample goal.
Validation of operation structure of the project
Validation of operation structure includes repository, data collection tools, logistics for intervention distribution (chemotherapy) to the participating sites, strategies for recruitment and stimulation of adherence to intervention and follow-ups.
Adherence rates to treatment allocated per patient
Objectify 85% or more of adherence rates during intervention.
Measure loss of follow-up per study protocol
Aiming at reaching up to 20% during follow-ups and identification of critical factors for loss of follow-up and suggesting mitigation strategies.

Secondary Outcome Measures

Progression-free survival
Description of overall rates (non-comparative between treatment groups) of progression-free survival.
Overall survival
Description of overall rates (non-comparative between treatment groups) of overall survival.
Response rate
Description of response rate via Response Evaluation Criteria In Solid Tumours (RECIST) criteria 1.1 2009.
Quality of life questionnaire
Description of quality of life via European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (QLC-C30) and a complementary module of the cervical cancer-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-CX24).
Adverse Events
Description of tolerance to proposed intervention, by creating a Data and Safety Monitoring Board (DSMB).

Full Information

First Posted
March 1, 2023
Last Updated
March 26, 2023
Sponsor
Hospital do Coracao
Collaborators
University of Sao Paulo
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1. Study Identification

Unique Protocol Identification Number
NCT05764044
Brief Title
Adjuvant Chemotherapy in cfHPV-DNA Plasma Positive Patients: A Biomarker In Locally Advanced Cervical Cancer
Acronym
AddChemo
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2023 (Anticipated)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
December 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital do Coracao
Collaborators
University of Sao Paulo

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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. Those with a negative qualitative research result will leave the study. Patients who have positive research for plasma 16/18 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 implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design. 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer, Cervix Cancer, Cervix Neoplasm
Keywords
Human papillomavirus, HPV, Cervical cancer, Circulating free DNA, Adjuvant chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
A prospective, randomized, multicenter, national, superiority, parallel, clinical trial, design to evaluate implementation components for conducting a national clinical trial using adjuvant chemotherapy in patients with locally advanced cervical cancer, selected by cfDNA-HPV biomarker. At the end of this pilot study, reaching feasibility goal, it is proposed to amplify size sample, with the same design. The participants will conduct a blood collection for research of cfDNA-HPV and will receive conventional treatment, gold standard currently, characterizing the descriptive phase of the research. In the second operational phase, it will happen the study randomization, designing an experimental study. The pilot study is scheduled to last one year and estimate the possibility to recruit between 30 and 50 patients during 2023.
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control Arm (Standard of Care)
Arm Type
Other
Arm Description
Patients will be followed with 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 Title
Experimental Arm
Arm Type
Experimental
Arm Description
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 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.
Intervention Type
Drug
Intervention Name(s)
cisplatin, gemcitabine
Intervention Description
Two additional cycles of cisplatin-based adjuvant chemotherapy 50mg/m2 D1 and gemcitabine 1000mg/m2 D1 and D8 at every 21 days.
Intervention Type
Other
Intervention Name(s)
Follow-up
Intervention Description
Patients will be followed with computed tomography (CT) scan of the thorax and magnetic resonance (MRI) of abdomen and pelvis and clinical and gynecological examination at every four months.
Primary Outcome Measure Information:
Title
Activation speed
Description
Accessing regulatory process, hiring and training of investigator sites.
Time Frame
30 days
Title
Eligibility profile for study of patients with cervical cancer
Description
Analyzing the impact of pandemic on disease diagnosis period.
Time Frame
120 days
Title
Potential for recruitment
Description
Potential for recruiting 4 to 12 patients/month in each investigator site is sufficient to reach sample goal.
Time Frame
210 days
Title
Validation of operation structure of the project
Description
Validation of operation structure includes repository, data collection tools, logistics for intervention distribution (chemotherapy) to the participating sites, strategies for recruitment and stimulation of adherence to intervention and follow-ups.
Time Frame
270 days
Title
Adherence rates to treatment allocated per patient
Description
Objectify 85% or more of adherence rates during intervention.
Time Frame
270 days
Title
Measure loss of follow-up per study protocol
Description
Aiming at reaching up to 20% during follow-ups and identification of critical factors for loss of follow-up and suggesting mitigation strategies.
Time Frame
270 days
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Description of overall rates (non-comparative between treatment groups) of progression-free survival.
Time Frame
210 days
Title
Overall survival
Description
Description of overall rates (non-comparative between treatment groups) of overall survival.
Time Frame
210 days
Title
Response rate
Description
Description of response rate via Response Evaluation Criteria In Solid Tumours (RECIST) criteria 1.1 2009.
Time Frame
210 days
Title
Quality of life questionnaire
Description
Description of quality of life via European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (QLC-C30) and a complementary module of the cervical cancer-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-CX24).
Time Frame
210 days
Title
Adverse Events
Description
Description of tolerance to proposed intervention, by creating a Data and Safety Monitoring Board (DSMB).
Time Frame
210 days

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3 to IVA will be included prospectively. Karnofsky performance status score ≥70, with estimated life expectancy ≥12 weeks, Immunocompetent, Positive research for types 16 or 18 cfHPV-DNA in plasma at diagnosis, Proper hematological, liver and kidney functions. Inclusion criteria will include absolute neutrophils count ≥1.5 x 109/L, platelets ≥100 x 10/L, hemoglobin ≥10,0 g/dL, serum bilirubin ≤ 2.0 x upper limit of normal (ULN), calculated creatinine clearance ≥60 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, Previous HPV vaccination with bivalent or superior vaccine, Period between start and end of chemoradiotherapy treatment superior to eight weeks, Inability to perform concurrent cisplatin based-chemoradiotherapy. Tumors containing different HPV genotypes of 16 or 18.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michelle S Almeida, PhD
Phone
11 999112805
Email
malmeida@hcor.com.br
First Name & Middle Initial & Last Name or Official Title & Degree
Rachel H Machado, MCS
Phone
11 30536611
Ext
8220
Email
rhelena@hcor.com.br
Facility Information:
Facility Name
Hospital do Coração - Research Institute
City
Sao Paulo
ZIP/Postal Code
04005-000
Country
Brazil
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle S Almeida, PhD
Phone
+5511 999112805
Email
malmeida@hcor.com.br
First Name & Middle Initial & Last Name & Degree
Michelle S Almeida, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data could be shared after reasonable request of the principal investigator.
IPD Sharing Time Frame
After study completion.

Learn more about this trial

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

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