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

Official title

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

Overview

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.

Detailed description

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

Interventions

• Radiation 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.
• Radiation 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.

Primary outcome measures

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

Secondary outcome measures (8)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking Union Medical College Hospital — Beijing

Identifiers

NCT: NCT07584161 · ARTISAN

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗