MH-ART vs CF-IMRT in Postoperative Cervical/Endometrial Cancer

Официальное название

A Multicenter, Non-Inferiority, Phase III Randomized Controlled Trial Comparing Moderately Hypofractionated Online Adaptive Radiotherapy（MH-ART） vs. Conventional Fractionated Intensity-Modulated Radiotherapy（CF-IMRT） in Postoperative Cervical Cancer and Endometrial Cancer

Обзор

This is an investigator-initiated, prospective, national multi-center, phase III, randomized, open-label, non-inferiority clinical study. The hypothesis is that using online adaptive radiotherapy technology for moderately fractionated radiotherapy in post-operative patients with cervical/endometrial cancer may reduce radiotherapy-related toxicity and improve quality of life while ensuring target coverage. The objective is to evaluate treatment-related toxicity and efficacy of moderately fractionated online adaptive radiotherapy compared to conventionally fractionated intensity-modulated radiotherapy in post-operative cervical and endometrial cancer patients, aiming to provide a more precise, convenient, and cost-effective treatment option for patients.

Подробное описание

Randomization:

Intervention Group: Moderately fractionated radiotherapy using online adaptive radiotherapy technology.

Control Group: Conventionally fractionated radiotherapy using image-guided intensity-modulated radiotherapy technology.

Stratification Factors for Randomization:Participating study center; Disease type (Cervical cancer / Endometrial cancer); Receipt of concurrent chemotherapy

Study Objectives:

Primary Endpoint: Acute adverse reactions/toxicity Secondary Endpoints: Late adverse reactions/toxicity, 3-year local control rate, 3-year distant metastasis rate, 3-year progression-free survival (PFS), 3-year overall survival (OS), 3-year disease-free survival (DFS), quality of life, cost-effectiveness analysis related to treatment.

Study Population:

Planned Sample Size: 228 participants

Inclusion Criteria:

1. Participants must be fully voluntary and have decision-making capacity, providing written informed consent within 30 days prior to enrollment. 2. Age ≥18 years and ≤75 years. 3. ECOG performance status of 0-1, and expected to tolerate lying supine for half an hour. 4. Have undergone radical surgery for cervical cancer (procedure: radical hysterectomy + pelvic lymphadenectomy ± para-aortic lymphadenectomy) or surgery for endometrial cancer (procedure: total hysterectomy + bilateral salpingo-oophorectomy ± pelvic and/or para-aortic lymph node dissection/sampling or sentinel lymph node biopsy). 5. For participants with cervical cancer, the following criteria must be met:

(1)Pathologically diagnosed with cervical squamous cell carcinoma or adenocarcinoma.

(2)Must have at least one of the following high-risk factors; or have other risk factors requiring postoperative radiotherapy: High-risk factors: Pelvic lymph node metastasis, or positive surgical margin, or parametrial invasion.

Other risk factors: Middle or deep one-third stromal invasion, regardless of tumor size and LVSI status; Tumor size ≥4cm, regardless of depth of stromal invasion and LVSI status; Adenocarcinoma: Tumor size ≥2cm, or positive LVSI, regardless of depth of stromal invasion.

6.For participants with endometrial cancer, the following criteria must be met: Endometrioid adenocarcinoma: Grade 3 with superficial myometrial invasion, accompanied by substantial LVSI or age ≥70 years; Grade 2 with deep myometrial invasion, accompanied by substantial LVSI or age ≥60 years; Grade 3 with deep myometrial invasion; FIGO 2009 Stage II-IIIC1.

Non-endometrioid adenocarcinoma: FIGO 2009 Stage I-IIIC1 (serous carcinoma, clear cell carcinoma, mixed type).

7.Participants with high-risk factors may receive a vaginal brachytherapy boost following the completion of external beam radiotherapy.

8.Participants with high-risk cervical cancer must receive concurrent sensitizing chemotherapy for ≥4 cycles.

9.Participants must be eligible to receive sequential or sandwich adjuvant chemotherapy as planned.

Study Duration: September 2025 to September 2030 Participant Involvement Period: Follow-up for over 3 years after radiotherapy

Вмешательства

• Лучевая терапия Moderately fractionated radiotherapy using online adaptive radiotherapy technology
  Treatment will be delivered using an online adaptive radiotherapy device. A moderately fractionated regimen will be employed, with a prescribed dose of 40.05 Gy in 15 fractions, administered once daily, five times per week.
• Лучевая терапия Conventionally fractionated radiotherapy using image-guided intensity-modulated radiotherapy technology.
  Intensity-modulated radiotherapy techniques will be used, including FF-IMRT, VMAT, or TOMO. A conventionally fractionated regimen will be employed, with a prescribed dose of 45 Gy in 25 fractions, administered once daily, five times per week.

Первичные конечные точки

• Incidence of Acute Toxicity [Срок оценки: Within 90 days (inclusive) from the start of radiotherapy]

Вторичные конечные точки (8)

• Incidence of Late Toxicity [Срок оценки: From 90 days after the start of radiotherapy until death from any cause, assessed up to 3 years.]
• 3 years Local Recurrence Rate [Срок оценки: From the end of radiotherapy until local recurrence or death from any cause, assessed up to 3 years.]
• 3 years Distant Metastasis Rate [Срок оценки: From the start of radiotherapy until distant metastasis or death from any cause, assessed up to 3 years.]
• 3 years Progression-Free Survival [Срок оценки: From the start of radiotherapy until the first disease recurrence (local/regional/distant) or death from any cause, assessed up to 3 years.]
• 3 years Overall Survival [Срок оценки: From the start of radiotherapy until death from any cause, assessed up to 3 years.]
• 3 years Disease-Free Survival [Срок оценки: From the start of radiotherapy until the first local/regional recurrence, distant metastasis, or death from any cause, assessed up to 3 years.]
• Quality of Life [Срок оценки: Baseline, at the end of radiotherapy, and every 3 months thereafter until 3 years from start of radiotherapy.]
• Treatment-Related Cost-Effectiveness Analysis [Срок оценки: From the start of radiotherapy until death from any cause, assessed up to 3 years.]

Критерии участия

Критерии включения

• Participants must be fully voluntary and have decision-making capacity, providing written informed consent within 30 days prior to enrollment.
• Age ≥18 years and ≤75 years.
• ECOG performance status of 0-1, and expected to tolerate lying supine for half an hour.
• Have undergone radical surgery for cervical cancer (procedure: radical hysterectomy + pelvic lymphadenectomy ± para-aortic lymphadenectomy) or surgery for endometrial cancer (procedure: total hysterectomy + bilateral salpingo-oophorectomy ± pelvic and/or para-aortic lymph node dissection/sampling or sentinel lymph node biopsy).
• For participants with cervical cancer, the following criteria must be met:

(1)Pathologically diagnosed with cervical squamous cell carcinoma or adenocarcinoma.

(2)Must have at least one of the following high-risk factors; or have other risk factors requiring postoperative radiotherapy: High-risk factors: Pelvic lymph node metastasis, or positive surgical margin, or parametrial invasion.

Other risk factors: Middle or deep one-third stromal invasion, regardless of tumor size and LVSI status; Tumor size ≥4cm, regardless of depth of stromal invasion and LVSI status; Adenocarcinoma: Tumor size ≥2cm, or positive LVSI, regardless of depth of stromal invasion.

6.For participants with endometrial cancer, the following criteria must be met: Endometrioid adenocarcinoma: Grade 3 with superficial myometrial invasion, accompanied by substantial LVSI or age ≥70 years; Grade 2 with deep myometrial invasion, accompanied by substantial LVSI or age ≥60 years; Grade 3 with deep myometrial invasion; FIGO 2009 Stage II-IIIC1.

Non-endometrioid adenocarcinoma: FIGO 2009 Stage I-IIIC1 (serous carcinoma, clear cell carcinoma, mixed type).

7.Participants with high-risk factors may receive a vaginal brachytherapy boost following the completion of external beam radiotherapy.

8.Participants with high-risk cervical cancer must receive concurrent sensitizing chemotherapy for ≥4 cycles.

9.Participants must be eligible to receive sequential or sandwich adjuvant chemotherapy as planned.

Критерии исключения

• Presence of confirmed distant metastasis or para-aortic lymph node metastasis;
• Requirement for extended-field radiotherapy encompassing the para-aortic region;
• Initiation of radiotherapy exceeds the specified time limit after surgery: exceeding 6 months post-surgery if adjuvant chemotherapy was administered, or exceeding 3 months post-surgery if no adjuvant chemotherapy was administered;
• History of previous abdominal or pelvic radiotherapy;
• History of or concurrent secondary primary malignancy (except for non-melanoma skin cancer, papillary/follicular thyroid carcinoma, or carcinoma in situ of the breast);
• History of underlying intestinal diseases such as ulcerative colitis or Crohn's disease;
• Cervical cancer with pathological types such as adenosquamous carcinoma, small cell carcinoma, clear cell carcinoma, or other special types; Endometrial cancer with pathological types such as undifferentiated carcinoma, carcinosarcoma, or other special types;
• Pregnant or lactating women;
• Presence of active infection or fever;
• Other severe comorbidities that may significantly compromise protocol compliance, such as uncontrolled cardiac disease requiring treatment, renal disease, chronic hepatitis, poorly controlled diabetes, psychiatric disorders, etc.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking Union Medical College Hospital — Пекин

Идентификаторы

NCT: NCT07584161 · ARTISAN

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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