PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer

Leiden University Medical Center30 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Uterine Cervical Neoplasms Locally Advanced Cervical Carcinoma

Interventions

External beam radiation therapy: IMRT/VMATRADIATION

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.

External beam radiation therapy: IMPTRADIATION

CisplatinDRUG

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

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Leiden University Medical Center

Leiden, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, Netherlands

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

Dmean to the pelvic bones

Mean dose to the pelvic bones (Gy).

Time frame: During treatment

Mean V15Gy to the bowel

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

Time frame: During treatment

Secondary Outcomes

Key dosimetric parameters of the bladder

Mean volume of the bladder (%) receiving greater than or equal to 15, 30, and 40Gy.

Time frame: During treatment

Key dosimetric parameters of the rectum

Mean volume of the rectum (%) receiving greater than or equal to 15, 30, and 40Gy.

Time frame: During treatment

Key dosimetric parameters of the sigmoid

Mean volume of the sigmoid (%) receiving greater than or equal to 15, 30, and 40Gy.

Time frame: During treatment

Key dosimetric parameters of the bowel

Mean volume of the bowel (cc) receiving greater than or equal to 30 and 40Gy.

Time frame: During treatment

Key dosimetric parameters of the body

Mean dose to the body (Gy) and mean volume of the body (cm3) receiving greater than or equal to 10 Gy.

Time frame: During treatment

Key dosimetric parameters of the pelvic bones

Mean volume of the pelvic bones (% or cc) receiving greater than or equal to 10, 20, and 40Gy.

Central Contacts

Anouk Corbeau, MSc

CONTACT

+31 71 529 7893 a.corbeau@lumc.nl

Stephanie M. de Boer, MD, PhD

CONTACT

+31 71 529 9380 s.m.de_boer.onco@lumc.nl

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.