Moderated Hypofractionated Online Adaptive Radiotherapy in Cervical Cancer

NCT06641635RecruitingPHASE3INTERVENTIONAL

Summary

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.

Key Facts

Lead Sponsor

Peking Union Medical College Hospital

Enrollment

440

Start Date

2024-11-19

Completion Date

2026-10-31

Study Type

INTERVENTIONAL

Official Title

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

Interventions

Moderated hypofractionated online adaptive radiotherapyConventional radiotherapy

Conditions

Cervical CancerAdaptive Radiotherapy

Eligibility

Age Range

18 Years – 75 Years

Sex

FEMALE

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.

Outcome Measures

Primary Outcomes

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.

Time frame: 3 years

Secondary Outcomes

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.

Time frame: 3 months

Late toxicity

Late toxicities will be collected from 3 months after completion of radiation onwards until the end of follow-up.

Time frame: 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.

Time frame: 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."

Time frame: 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).

Time frame: 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.

Time frame: 3 years

Tumor response evaluation Complete remission rate

Evaluated with RECIST 1.1

Time frame: 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.

Time frame: 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.

Time frame: 3 years

Treatment expense

The treatment-related costs incurred during the course of treatment.

Time frame: 3 months

Locations

Peking Union Medical College Hospital, Beijing, China

Linked Papers

2025-07-16

Moderately hypofractionated online adaptive radiotherapy (SWIFT-1) in cervical cancer patients: study protocol for a multi-centered, open-label, two-arm, phase III, randomized controlled study

External beam radiotherapy (EBRT) is an essential component of standard treatment for locally advanced cervical cancer. Moderately hypofractionated radiotherapy (MHRT) offers the potential to reduce treatment burden while compromising efficacy. Although various studies have investigated the safety and efficacy of MHRT, high-quality evidence remains inadequate. The lack of integration of modern radiotherapy techniques in many existing studies may lead to an overestimation of MHRT-associated toxicity. This prospective, multi-center, randomized controlled, non-inferiority phase III trial aims to evaluate the non-inferiority of moderately hypofractionated online adaptive radiotherapy (oART) compared to conventional fractionated radiotherapy (CFRT). A total of 440 participants will be enrolled and randomly assigned in a 1:1 ratio to either the MHRT or CFRT group. Both groups will receive concurrent chemoradiotherapy, and a subset of eligible patients will undergo immunotherapy. The prescribed EBRT dose for the MHRT group will be 43.35 Gy in 17 fractions, with a simultaneous integrated boost of 54.4 Gy in 17 fractions to positive lymph nodes. The CFRT group will receive 45 Gy in 25 fractions, with a simultaneous integrated boost of 60 Gy in 25 fractions to positive lymph nodes. The primary endpoint will be 3-year progression-free survival. Secondary endpoints will include the complete response rate, tumor regression following EBRT, overall survival, locoregional progression-free survival, metastasis-free survival, cervical cancer-specific survival, acute and late toxicity, and quality of life. This randomized controlled trial will prospectively investigate whether MHRT is non-inferior to conventional fractionation in terms of efficacy and safety. Furthermore, the trial will evaluate the potential of moderately hypofractionated oART as a clinically viable alternative to CFRT for the treatment of locally advanced cervical cancer. This trial was registered at ClincalTrials.gov (NCT06641635) on October 12, 2024.

Linked Investigators

Fu-Quan Zhang

Junfang Yan

Ke Hu