Clinical trial NCT05406856: PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer
Official title: PROTECT: On-line Adaptive Proton Therapy for Cervical Cancer to Reduce the Impact on Morbidity and the Immune System
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Uterine Cervical Neoplasms
Locally Advanced Cervical Carcinoma
Keywords: Non-randomized phase-II trial
Primary chemoradiotherapy
Proton therapy
Organ sparing therapy
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: HollandPTC
First posted: 2022-06-07
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dmean to the pelvic bones
timeFrame: During treatment
measure: Mean V15Gy to the bowel
timeFrame: During treatment
Secondary outcomes:
measure: Key dosimetric parameters of the bladder
timeFrame: During treatment
measure: Key dosimetric parameters of the rectum
timeFrame: During treatment
measure: Key dosimetric parameters of the sigmoid
timeFrame: During treatment
measure: Key dosimetric parameters of the bowel
timeFrame: During treatment
measure: Key dosimetric parameters of the body
timeFrame: During treatment
measure: Key dosimetric parameters of the pelvic bones
timeFrame: During treatment
measure: Key dosimetric parameter of the kidneys
timeFrame: During treatment
measure: Key dosimetric parameters of the spinal cord
timeFrame: During treatment
measure: Other dosimetric parameters of critical organs
timeFrame: During treatment
measure: Overall survival
timeFrame: At Month 12 after end of treatment
measure: Complete response
timeFrame: At Month 3 after end of treatment
measure: Pelvic recurrence-free survival
timeFrame: At Month 12 after end of treatment
measure: Distant recurrence-free survival
timeFrame: At Month 12 after end of treatment
measure: Health-related Quality of Life
timeFrame: At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment
measure: Safety and tolerability (toxicity)
timeFrame: At baseline, week 4 of EBRT, end of treatment, and at Month 3, Month 6, Month 9, and Month 12 after end of treatment
measure: The effect on the local immune system (analyzed with the Nanostring PanCancer IO 360 panel)
timeFrame: At baseline and at the first brachytherapy session
measure: The effect on the systemic immune system
timeFrame: At baseline, week 4 of treatment, and at Month 1, Month 2, Month 3, and Month 12 after end of treatment
measure: The effect on bone marrow fat fraction
timeFrame: At baseline, for brachytherapy purposes, and at Month 3 and Month 12 after end of treatment.
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Stephanie M. de Boer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.