Moderated Hypofractionated Online Adaptive Radiotherapy in Cervical Cancer

A Multicenter, Non-inferiority, Phase 3, Randomized Controlled Study of Moderated Hypofractionated Online Adaptive Radiotherapy for Cervical Cancer

The most common external beam radiotherapy fractionation scheme for cervical cancer is 45-50.4 Gy delivered in 25-28 fractions. However, prolonged treatment duration can lead to insufficient availability of medical resources. We hope to assess the safety and efficacy of moderated hypofractionated online adaptive radiotherapy in combination with brachytherapy in patients with cervical cancer in a multicenter study.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; Adaptive Radiotherapy
• Intervention / Treatment: Combination product: Moderated hypofractionated online adaptive radiotherapy; Combination product: Conventional radiotherapy

Detailed Description

This is a multicenter, non-inferiority, phase 3, randomized controlled study. This study investigates the role of moderated hypofractionated online adaptive radiotherapy by randomizing patients to this experimental regimen versus the standard of treatment.The purpose of this study is to access safety and efficacy of moderated hypofractionated online adaptive radiotherapy in combination with high-dose-rate brachytherapy in patients with cervical cancer, which based on the previous research (NCT05994300).

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zheng Zeng, MD.; Phone Number: 86-10-6512-4875; Email: zengzheng1206@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Junfang Yan, MD; Phone Number: 01069155484; Email: yanjunfang@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient is fully voluntary and has the capacity for autonomy, signing the informed consent form 30 days prior to enrollment
2. Age ≥18 and ≤75 years
3. FIGO stage IB-IIIB cervical cancer; IIIC1 (lymph node metastasis ≤2 cm, without common iliac lymph node metastasis)
4. Pathologically diagnosed as squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma
5. Concurrent weekly cisplatin therapy ± immunotherapy
6. Able to undergo brachytherapy
7. ECOG performance status of 0-1, with an expected ability to tolerate lying flat for half an hour.

Exclusion Criteria:

1. Patients who have undergone cervical cancer surgery, excluding pelvic lymphadenectomy or pelvic lymph node dissection, or cervical conization
2. FIGO stages IA, IIIC2, IVA, or IVB
3. FIGO stage IIIC1 with lymph nodes >2 cm, or with common iliac lymph node metastasis
4. History of prior abdominal or pelvic radiotherapy
5. Pregnant or breastfeeding women
6. Patients with active infections or fever
7. Other severe diseases that may significantly affect clinical trial compliance, such as unstable heart disease, kidney disease, chronic hepatitis requiring treatment, poorly controlled diabetes, or mental disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Radiotherapy +Concurrent Chemotherapy or Immunotherapy Experimental	Combination product: Moderated hypofractionated online adaptive radiotherapy; Radiation: Moderated hypofractionated online adaptive radiotherapy (oART)+ High-dose rate (HDR) Brachytherapy Experimental group: 43.35Gy/17F external beam radiotherapy with oART + HDR-Brachytherapy Drug: Concurrent Chemotherapy or immunotherapy Weekly cisplatin 40 mg/m2 or PD-1 inhibitors
Active Comparator: Control group; Radiotherapy +Concurrent Chemotherapy or Immunotherapy Standard of Care	Combination product: Conventional radiotherapy; Radiation: External beam radiotherapy (EBRT) + High-dose rate (HDR) Brachytherapy Contral group: 45Gy/25F EBRT + HDR-Brachytherapy Drug: Concurrent Chemotherapy or immunotherapy Weekly cisplatin 40 mg/m2 or PD-1 inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Defined as time from date of randomization to date of progression, date of death from any cause, or date of last follow-up, whichever occurs first. Cancer progression can be identified during physical exam, biopsy, or imaging of any kind.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicity	This outcome is assessed by physicians during each follow-up appointment, and scored according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 . Clinically relevant toxicities of gastrointestinal, genitourinary, vaginal and non-specific general symptoms (i.e. fatigue, malaise and pain) will be collected. Hematological disorders will also be collected through weekly blood work checks. Acute toxicities will be collected at baseline, and then weekly during radiotherapy/chemoradiotherapy and at 3 months after completion of radiation.	3 months
Late toxicity	Late toxicities will be collected from 3 months after completion of radiation onwards until the end of follow-up.	3 years
Overall survival	Defined as time from date of randomization to date of death from any cause, or date of last follow-up, whichever occurs first.	3 years
Quality of life (QoL)	QoL will evaluated by the EORTC QLQ-C30 questionnaire.QLQ-C30 questionnaire is used for all cancers and has several symptom scales, five functional scales (physical, emotional, social, role, cognitive) and a global health status scale. Response options are a four-point Likert scale from "not at all" to "very much" or a seven-point Likert scale from "very poor" to "excellent."	3 years
Quality of Life (QoL)	QoL will be measured by the cervical cancer module (QLQ-CX24). QLQ-CX24 includes cancer - and treatment - related items and symptoms regarding sexuality. Acute and late vaginal and sexual QoL will be assessed using the QLQ-CX24 vaginal and sexual domains respectively. The QLQ-CX24 responses are regarding function and symptoms of sexual and vagina health. It is based on a scale of 1 (not at all) to 4 (very much).	3 years
Locoregional progression-free survival	Defined as time from date of randomization to date of locoregional progression, date of death from any cause, or date of last follow-up, whichever occurs first.	3 years
Tumor response evaluation Complete remission rate	Evaluated with RECIST 1.1	3 months
Treatment expense	The treatment-related costs incurred during the course of treatment.	3 months
Metastasis-free survival	Defined as time from date of randomization to date of development of metastasis, date of death from any cause, or date of last follow-up, whichever occurs first.	3 years
Cervical cancer-specific survival	Defined as time from date of randomization to date of death attributed to cervical cancer, or date of last-follow-up, whichever occurs first.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of tumor regression throughout EBRT	To be assessed through volumetric comparison of tumor volume in the pre-EBRT and post-EBRT MRI scans.	3 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Peking University Cancer Hospital & Institute; Ruijin Hospital; Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: October 8, 2024
• First Submitted That Met QC Criteria: October 12, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Cervical Cancer; Adaptive Radiotherapy; Moderated Hypofractionated Radiotherapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: SWIFT-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes