NCT05406856

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for not_applicable

Timeline
7mo left

Started May 2022

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress88%
May 2022Dec 2026

Study Start

First participant enrolled

May 2, 2022

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

May 11, 2022

Completed
27 days until next milestone

First Posted

Study publicly available on registry

June 7, 2022

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2025

Completed
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2026

Expected
Last Updated

October 11, 2023

Status Verified

October 1, 2023

Enrollment Period

3.2 years

First QC Date

May 11, 2022

Last Update Submit

October 10, 2023

Conditions

Keywords

Non-randomized phase-II trialPrimary chemoradiotherapyProton therapyOrgan sparing therapy

Outcome Measures

Primary Outcomes (2)

  • Dmean to the pelvic bones

    Mean dose to the pelvic bones (Gy).

    During treatment

  • Mean V15Gy to the bowel

    Mean volume of the bowel (cc) receiving 15Gy.

    During treatment

Secondary Outcomes (18)

  • Key dosimetric parameters of the bladder

    During treatment

  • Key dosimetric parameters of the rectum

    During treatment

  • Key dosimetric parameters of the sigmoid

    During treatment

  • Key dosimetric parameters of the bowel

    During treatment

  • Key dosimetric parameters of the body

    During treatment

  • +13 more secondary outcomes

Study Arms (2)

IMRT/VMAT group

ACTIVE COMPARATOR

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/VMATDrug: CisplatinRadiation: Brachytherapy

IMPT group

EXPERIMENTAL

This group receives curative treatment with primary external beam radiation therapy (IMPT), combined with chemotherapy, followed by 3D image (MRI)-guided adaptive brachytherapy.

Radiation: External beam radiation therapy: IMPTDrug: CisplatinRadiation: Brachytherapy

Interventions

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.

Also known as: Intensity Modulated Radiation Therapy, Volumetric Modulated Arc Therapy
IMRT/VMAT group

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.

Also known as: Intensity Modulated Proton Therapy
IMPT group

The standard chemotherapy regimen is weekly cisplatin (40 mg/m2) for 5 weeks.

IMPT groupIMRT/VMAT group
BrachytherapyRADIATION

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.

IMPT groupIMRT/VMAT group

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, 3015 GD, Netherlands

NOT YET RECRUITING

Related Publications (1)

  • Corbeau A, Nout RA, Mens JWM, Horeweg N, Godart J, Kerkhof EM, Kuipers SC, van Poelgeest MIE, Kroep JR, Boere IA, van Doorn HC, Hoogeman MS, van der Heide UA, Putter H, Welters MJP, van der Burg SH, Creutzberg CL, de Boer SM. PROTECT: Prospective Phase-II-Trial Evaluating Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System. Cancers (Basel). 2021 Oct 15;13(20):5179. doi: 10.3390/cancers13205179.

    PMID: 34680328BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Radiotherapy, Intensity-ModulatedCisplatinBrachytherapy

Condition Hierarchy (Ancestors)

Uterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, ConformalRadiotherapy, Computer-AssistedRadiotherapyTherapeuticsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum Compounds

Study Officials

  • Stephanie M. de Boer, MD, PhD

    Leiden University Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Anouk Corbeau, MSc

CONTACT

Stephanie M. de Boer, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: The study is designed as a prospective, multicenter, nonrandomized phase-II-trial. During the first phase of the trial, 15 patients will be enrolled in the IMRT/VMAT treatment group. In the second phase of the trial, 15 patients will be enrolled in the IMPT group.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
prof., dr.

Study Record Dates

First Submitted

May 11, 2022

First Posted

June 7, 2022

Study Start

May 2, 2022

Primary Completion

July 1, 2025

Study Completion (Estimated)

December 1, 2026

Last Updated

October 11, 2023

Record last verified: 2023-10

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, CSR
Time Frame
After final publication
Access Criteria
Approval by the trial management group is necessary

Locations