RecruitingNot ApplicableNCT05406856

PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer

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

Sponsor

Leiden University Medical Center

Enrollment

30 participants

Start Date

May 2, 2022

Study Type

INTERVENTIONAL

Conditions

Uterine Cervical Neoplasms Locally Advanced Cervical Carcinoma

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.

Eligibility

Sex: FEMALEMin Age: 18 Years

Inclusion Criteria10

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 Criteria11

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

Interventions

RADIATIONExternal 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.

RADIATIONExternal beam radiation therapy: IMPT

DRUGCisplatin

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

RADIATIONBrachytherapy

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.