PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer (PROTECT)

October 10, 2023 updated by: Carien Creutzberg, Leiden University Medical Center

PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System

This prospective, multicenter, nonrandomized phase-II-trial investigates in clinical practice the differences between intensity modulated proton therapy (IMPT) and standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) in the effects on dose-volume parameters and treatment-related morbidity for women with locally advanced cervical cancer undergoing chemoradiation.

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

External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a highly effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient's quality of life (QoL) and may affect ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). However, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy. Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.

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.
30

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.
  • Not Applicable

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

  • Netherlands
      • Leiden, Netherlands, 2333 ZA
        • Recruiting
        • Leiden University Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Stephanie M. de Boer, MD, PhD
        • Sub-Investigator:
          • Anouk Corbeau, MSc
      • Rotterdam, Netherlands, 3015 GD
        • Not yet recruiting
        • Erasmus Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Remi A. Nout, professor

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed diagnosis of cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, HPV positive or negative) with an indication for curative treatment with primary chemoradiation with concurrent cisplatin followed by 3D image-guided adaptive brachytherapy.
  • Indication to include the common iliac region (minimum 5, maximum 8) or the common iliac and para-aortic regions (minimum 7, maximum 10) into the elective clinical target volume of the external beam radiotherapy.
  • No distant metastasis beyond the para-aortic lymph node chain as determined by diagnostic imaging (CT or PET-CT scan)
  • Age ≥ 18 years
  • WHO 0-1

  • Adequate systemic organ function:

    • Creatinine clearance (> 50 cc/min)
    • Adequate bone marrow function : white blood cells (WBCs) ≥3.0 x 109/l, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l
  • Patients must be accessible for treatment and follow-up
  • Written informed consent according to the local Ethics Committee requirements

Exclusion Criteria:

  • Small cell cancer, melanoma and other rare histological types of the cervix.

  • History of another primary malignancy that could conceivably be active evaluated by the study physician. Examples of exception include, but are not limited to:

    • Malignancy treated with curative intent and with no known active disease ≥5 years.
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
  • Other severe diseases such as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias
  • Previous pelvic or abdominal radiotherapy
  • History of active primary immunodeficiency
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g. colitis or Crohn's disease])
  • The use of immunosuppressive drugs at baseline
  • Contraindications for weekly Cisplatin (or Carboplatin)
  • Contraindications for the use of MRI

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

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.
Active Comparator: IMRT/VMAT group
This group receives standard of care curative treatment with primary external beam radiation therapy (IMRT/VMAT), combined with chemotherapy, followed by 3D image (MRI)-guided adaptive brachytherapy.
Radiation: External beam radiation therapy: IMRT/VMAT
EBRT is given to a total dose of 45 Gy in 25 daily fractions of 1.8 Gy in 5 weeks. Involved nodes are boosted using a simultaneous integrated boost (SIB) to reach a total EBRT plus brachytherapy dose of 60 Gy EQD2 to provide high nodal control.
Other Names:
  • Intensity Modulated Radiation Therapy
  • Volumetric Modulated Arc Therapy
Drug: Cisplatin
The standard chemotherapy regimen is weekly cisplatin (40 mg/m2) for 5 weeks.
Radiation: Brachytherapy
Brachytherapy is performed using a high-dose rate (HDR) after loading system to deliver a boost to any residual tumor and the cervix. Brachytherapy dose is (21-) 28 Gy in fractions of 7 Gy specified at 100% isodose around the high-risk CTV, according to the EMBRACE-II prescription protocol. The aim is to reach an equivalent dose in 2 Gy fractions including EBRT (EQD2_D90) of the high-risk CTV between 90-95 Gy, using MRI-guided adaptive brachytherapy.
Experimental: IMPT group
This group receives curative treatment with primary external beam radiation therapy (IMPT), combined with chemotherapy, followed by 3D image (MRI)-guided adaptive brachytherapy.
Drug: Cisplatin
The standard chemotherapy regimen is weekly cisplatin (40 mg/m2) for 5 weeks.
Radiation: Brachytherapy
Brachytherapy is performed using a high-dose rate (HDR) after loading system to deliver a boost to any residual tumor and the cervix. Brachytherapy dose is (21-) 28 Gy in fractions of 7 Gy specified at 100% isodose around the high-risk CTV, according to the EMBRACE-II prescription protocol. The aim is to reach an equivalent dose in 2 Gy fractions including EBRT (EQD2_D90) of the high-risk CTV between 90-95 Gy, using MRI-guided adaptive brachytherapy.
Radiation: External beam radiation therapy: IMPT
EBRT is given to a total dose of 45 Gy in 25 daily fractions of 1.8 Gy in 5 weeks. Involved nodes are boosted using a simultaneous integrated boost (SIB) to reach a total EBRT plus brachytherapy dose of 60 Gy EQD2 to provide high nodal control.
Other Names:
  • Intensity Modulated Proton Therapy

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
Dmean to the pelvic bones
Time Frame: During treatment
Mean dose to the pelvic bones (Gy).
During treatment
Mean V15Gy to the bowel
Time Frame: During treatment
Mean volume of the bowel (cc) receiving 15Gy.
During treatment

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
Key dosimetric parameters of the bladder
Time Frame: During treatment
Mean volume of the bladder (%) receiving greater than or equal to 15, 30, and 40Gy.
During treatment
Key dosimetric parameters of the rectum
Time Frame: During treatment
Mean volume of the rectum (%) receiving greater than or equal to 15, 30, and 40Gy.
During treatment
Key dosimetric parameters of the sigmoid
Time Frame: During treatment
Mean volume of the sigmoid (%) receiving greater than or equal to 15, 30, and 40Gy.
During treatment
Key dosimetric parameters of the bowel
Time Frame: During treatment
Mean volume of the bowel (cc) receiving greater than or equal to 30 and 40Gy.
During treatment
Key dosimetric parameters of the body
Time Frame: During treatment
Mean dose to the body (Gy) and mean volume of the body (cm3) receiving greater than or equal to 10 Gy.
During treatment
Key dosimetric parameters of the pelvic bones
Time Frame: During treatment
Mean volume of the pelvic bones (% or cc) receiving greater than or equal to 10, 20, and 40Gy.
During treatment
Key dosimetric parameter of the kidneys
Time Frame: During treatment
Mean dose to the kidneys (Gy).
During treatment
Key dosimetric parameters of the spinal cord
Time Frame: During treatment
Mean volume of the spinal cord (%) receiving greater than or equal to 15 and 30Gy.
During treatment
Other dosimetric parameters of critical organs
Time Frame: During treatment
Mean volume of an organ at risk (% or cc) receiving greater than or equal to xGy.
During treatment
Overall survival
Time Frame: At Month 12 after end of treatment
The percentage (%) of included patients who are alive after start of treatment
At Month 12 after end of treatment
Complete response
Time Frame: At Month 3 after end of treatment
Absence of disease in the cervix, uterus, upper vagina, and parametria.
At Month 3 after end of treatment
Pelvic recurrence-free survival
Time Frame: At Month 12 after end of treatment
The time from start of treatment to the first occurrence of pelvic recurrence.
At Month 12 after end of treatment
Distant recurrence-free survival
Time Frame: At Month 12 after end of treatment
The time from start of treatment to the first occurrence of distant recurrence.
At Month 12 after end of treatment
Health-related Quality of Life
Time Frame: At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment
For the evaluation of patient reported symptoms and QoL, the European Organization for Research and Treatment of Cancer (EORTC)-core (C-30) questionnaire, the CX24 module for cervical cancer, and six additional questions from EN24 module will be used.
At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment
Safety and tolerability (toxicity)
Time Frame: At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment
Toxicity will be graded according to the NCI-CTCAE version 5.0.
At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment
The effect on the local immune system (analyzed with the Nanostring PanCancer IO 360 panel)
Time Frame: At baseline and at the first brachytherapy session
Tumor biopsies will be collected for evaluation of the impact of treatment on the local immune response.
At baseline and at the first brachytherapy session
The effect on the systemic immune system
Time Frame: At baseline, week 4 of treatment, and at Month 1, Month 2, Month 3, and Month 12 after end of treatment
Blood samples will be collected for immune-monitoring. Full blood count, peripheral blood mononuclear cells, leukocyte differentiation, APC quality, T cell reactivity, and immune composition changes will be measured.
At baseline, week 4 of treatment, and at Month 1, Month 2, Month 3, and Month 12 after end of treatment
The effect on bone marrow fat fraction
Time Frame: At baseline, for brachytherapy purposes, and at Month 3 and Month 12 after end of treatment.
Patients will have an MR scan with Dixon technique for evaluation of bone marrow fat fraction in the vertebral column and femoral necks.
At baseline, for brachytherapy purposes, and at Month 3 and Month 12 after end of treatment.

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.
Leiden University Medical Center

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.
Erasmus Medical Center
HollandPTC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Stephanie M. de Boer, MD, PhD, Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.
May 2, 2022

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.
July 1, 2025

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 1, 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).
May 11, 2022

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.
June 1, 2022

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.
June 7, 2022

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.
October 11, 2023

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.
October 10, 2023

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.
October 1, 2023

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.
  • NL77911.058.21

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After completion of the trial and publication of the final results, data will be available upon request with a scientific proposal. Approval by the trial management group is necessary.

IPD Sharing Time Frame

After final publication

IPD Sharing Access Criteria

Approval by the trial management group is necessary

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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