PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer

Leiden University Medical Center (LUMC)

Status: Enrolling

Conditions: Locally Advanced Cervical Carcinoma; Uterine Cervical Neoplasms

Treatments: Radiation: External beam radiation therapy: IMRT/VMAT; Drug: Cisplatin; Radiation: External beam radiation therapy: IMPT; Radiation: Brachytherapy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05406856

NL77911.058.21

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

IMRT/VMAT group

Active Comparator group

Description:

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.

Treatment:

Radiation: Brachytherapy

Drug: Cisplatin

Radiation: External beam radiation therapy: IMRT/VMAT

IMPT group

Experimental group

Description:

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

Treatment:

Radiation: Brachytherapy

Radiation: External beam radiation therapy: IMPT

Drug: Cisplatin