Hypofractionated Chemoradiotherapy for Cervical Cancer (HYPOCx)
HYPOfractionated Whole Pelvic Concurrent Chemoradiotherapy in Cervical Cancer (HYPOCx Trial): A Phase III Randomized Controlled Trial
The goal of this clinical trial is to evaluate whether hypofractionated whole pelvic or extended-field concurrent chemoradiotherapy can improve treatment access and efficiency while potentially providing superior oncologic efficacy and safety compared to conventional chemoradiotherapy in patients with early-stage node-positive and locally advanced cervical cancer. Building on encouraging safety and efficacy outcomes from our Phase II HYPOCx-iRex trial (TCTR20210812003), this study will provide data for a critical evidence gap regarding the safety, feasibility, and oncologic efficacy of hypofractionated radiotherapy, including extended-field para-aortic treatment, delivered with concurrent chemotherapy.
The main questions it aims to answer are:
- Does hypofractionated chemoradiotherapy achieve superior nodal control compared to conventional chemoradiotherapy?
- Does hypofractionated chemoradiotherapy achieve superior overall survival compared to conventional chemoradiotherapy?
Researchers will compare patients receiving hypofractionated external beam radiotherapy to those receiving conventional fractionation to evaluate if the shortened hypofractionated schedule provides comparable disease control, acceptable toxicity, improved quality of life, and cost-effectiveness.
Participants will:
- Be randomized to receive either hypofractionated external beam radiotherapy or conventional fractionation radiotherapy, both delivered using modern IMRT/VMAT techniques targeting either the whole pelvis or extended fields (including para-aortic lymph nodes).
- Receive concurrent platinum-based chemotherapy during external beam radiation.
- Complete image-guided adaptive brachytherapy following external beam radiotherapy.
- Attend scheduled follow-up visits to evaluate tumor response, disease control, treatment-related toxicities, quality of life, and survival outcomes.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
Cervical cancer remains a major contributor to cancer-related morbidity and mortality among women in low- and middle-income countries, including Thailand. Despite advancements in screening programs and human papillomavirus (HPV) vaccination, a substantial proportion of patients present with locally advanced disease necessitating definitive concurrent chemoradiotherapy.
The established standard of care for locally advanced cervical cancer consists of conventionally fractionated external beam radiotherapy (45 to 50.4 Gy delivered in 25 to 28 fractions) administered concurrently with platinum-based chemotherapy, followed by image-guided adaptive brachytherapy. However, this extended 5-to-7-week regimen imposes significant logistical and financial burdens on patients and healthcare infrastructure, contributing to prolonged overall treatment times, institutional capacity constraints, and restricted access to radiation oncology services. Although hypofractionated radiotherapy has established efficacy and safety in the treatment of breast, prostate, and rectal malignancies, high-level prospective evidence validating its application alongside concurrent chemotherapy in cervical cancer, particularly in the setting of extended-field irradiation, remains limited due to concerns regarding exacerbated gastrointestinal and hematologic toxicities.
To address these therapeutic constraints of conventional fractionation, our group conducted the Phase II HYPOCx-iRex trial (TCTR20210812003). Findings from the HYPOCx-iRex study provided essential clinical proof-of-concept, demonstrating that hypofractionated chemoradiotherapy delivered via advanced delivery techniques, such as IMRT/VMAT with adaptive brachytherapy, achieves acceptable gastrointestinal toxicity rates and promising short-term disease control relative to historical conventional benchmarks.
Building upon the foundation of the Phase II HYPOCx-iRex trial (TCTR20210812003), this multicenter Phase III randomized controlled superiority trial is designed to evaluate this hypofractionated paradigm. Crucially, this trial seeks to address the persistent lack of prospective evidence regarding the safety, feasibility, and oncologic efficacy of hypofractionated extended-field radiotherapy combined with concurrent platinum-based chemotherapy.
In this trial, patients with early-stage node-positive or locally advanced cervical cancer will be randomized to receive either hypofractionated or conventionally fractionated external beam radiotherapy, both administered using high-precision IMRT/VMAT techniques with concurrent chemotherapy and image-guided adaptive brachytherapy. The primary endpoints are nodal control and overall survival. Secondary endpoints encompass tumor response rate, locoregional control, event-free survival, acute and late toxicities, quality of life, and health economic cost-effectiveness. The trial's findings are anticipated to generate high-level clinical evidence capable of demonstrating superior therapeutic and operational value, mitigating treatment delays, and establishing a more accessible, resource-efficient treatment standard.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 3단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Tissana Prasartseree, MD
- 전화번호: 66625246101
- 이메일: tissana.p@gmail.com
연구 연락처 백업
- 이름: Pittaya Dankulchai, MD
- 전화번호: 66966233606
- 이메일: pittaya.dan@mahidol.ac.th
연구 장소
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Bangkok
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Bangkok Noi, Bangkok, 태국, 10700
- 모병
- Siriraj Hospital
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연락하다:
- Tissana Prasartseree, MD
- 전화번호: 66625246101
- 이메일: tissana.p@gmail.com
-
-
참여기준
자격 기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
- Cancer of the uterine cervix considered suitable for curative treatment with definitive radio-(chemo)therapy including imaged-guided BT
- Positive biopsy showing squamous-cell carcinoma, adenocarcinoma, or adeno-squamous cell carcinoma of the uterine cervix
- Locally advanced staging according to FIGO 2018 and TNM guidelines (Stage IA1-IVA)
- MRI of the pelvis at diagnosis is performed
- MRI, CT, or PET-CT of the retroperitoneal space and abdomen at diagnosis is performed
- MRI with the applicator in place at the time of (first) BT will be performed
- GFR ≥ 50 mL/min
- Patient informed consent
Exclusion Criteria:
- Other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin
- Small cell neuroendocrine cancer, melanoma and other rare cancers in the cervix
- Metastatic disease beyond intervertebral disc L2/3 level
- Previous pelvic or abdominal radiotherapy
- Previous total or subtotal hysterectomy
- Combination of preoperative radiotherapy with surgery
- Patients receiving BT only
- Patients receiving EBRT only
- Patients receiving neo-adjuvant chemotherapy or other forms of antineoplastic treatment apart from weekly concomitant cisplatin (40 mg/m2).
- Contra-indications to MRI
- Contra-indications to BT
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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활성 비교기: Conventional Chemoradiotherapy (CONV)
Participants assigned to this arm will receive conventionally fractionated whole pelvic external beam radiotherapy (45 Gy in 25 fractions or equivalent institutional standard) using IMRT/VMAT techniques, administered concurrently with weekly platinum-based chemotherapy, followed by image-guided adaptive brachytherapy according to institutional protocols.
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Whole pelvic external beam radiotherapy delivered using IMRT or VMAT techniques at a dose of 45 Gy in 25 fractions (1.8 Gy per fraction), administered once daily, five fractions per week.
Treatment is given concurrently with weekly platinum-based chemotherapy and followed by image-guided adaptive brachytherapy according to institutional protocols.
Concurrent chemotherapy once a week Cisplatin-based concurrent chemotherapy administered intravenously at a dose of 40 mg/m² once weekly during external beam radiotherapy for 5 to 6 cycles.
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실험적: Hypofractionated Chemoradiotherapy (HYPO)
Participants assigned to this arm will receive hypofractionated whole pelvic external beam radiotherapy (44 Gy in 20 fractions) using IMRT/VMAT techniques, administered concurrently with weekly platinum-based chemotherapy, followed by image-guided adaptive brachytherapy according to institutional protocols.
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Concurrent chemotherapy once a week Cisplatin-based concurrent chemotherapy administered intravenously at a dose of 40 mg/m² once weekly during external beam radiotherapy for 5 to 6 cycles.
Whole pelvic external beam radiotherapy delivered using IMRT or VMAT techniques at a dose of 44 Gy in 20 fractions (2.2 Gy per fraction), administered once daily, five fractions per week.
Treatment is given concurrently with weekly platinum-based chemotherapy and followed by image-guided adaptive brachytherapy according to institutional protocols.
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연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Nodal Recurrence-free Survival
기간: Up to 5 years after completion of radiotherapy
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Time from completion of radiotherapy to the first occurrence of nodal recurrence
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Up to 5 years after completion of radiotherapy
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Overall Survival (OS)
기간: Up to 5 years after completion of radiotherapy
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Time from completion of radiotherapy to death from any cause.
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Up to 5 years after completion of radiotherapy
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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Local Recurrence-free Survival
기간: At 3 and 5 years after completion of radiotherapy
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Time from completion of radiotherapy to local tumor recurrence.
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At 3 and 5 years after completion of radiotherapy
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Incremental Cost-effectiveness Ratio per Quality-adjusted Life Year Between Hypofractionated and Conventional Radiotherapy
기간: During treatment and follow-up up to 5 years after completion of radiotherapy.
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Cost and utility data will be used to evaluate cost-effectiveness by calculating the incremental cost-effectiveness ratio (ICER) between hypofractionated and conventional radiotherapy.
Uncertainty analyses will be performed using oneway sensitivity analysis, probabilistic sensitivity analysis, and threshold analysis.
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During treatment and follow-up up to 5 years after completion of radiotherapy.
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Tumor Response Rate
기간: Up to 12 months after completion of radiotherapy
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Tumor response rate assessed after external beam radiotherapy and at 3-, 6-, and 12-month follow-up after treatment.
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Up to 12 months after completion of radiotherapy
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Pelvic Recurrence-free Survival
기간: At 3 and 5 years after completion of radiotherapy
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Time from completion of radiotherapy to pelvic recurrence.
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At 3 and 5 years after completion of radiotherapy
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Para-aortic Recurrence-free Survival
기간: At 3 and 5 years after completion of radiotherapy
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Time from completion of radiotherapy to para-aortic recurrence.
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At 3 and 5 years after completion of radiotherapy
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Locoregional Recurrence-free Survival
기간: At 3 and 5 years after completion of radiotherapy
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Time from completion of radiotherapy to local, pelvic, or para-aortic recurrence.
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At 3 and 5 years after completion of radiotherapy
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Distant Metastasis-free Survival
기간: At 3 and 5 years after completion of radiotherapy
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Time from completion of radiotherapy to distant metastasis.
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At 3 and 5 years after completion of radiotherapy
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Event-free Survival
기간: Up to 5 years after completion of radiotherapy
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Time from completion of radiotherapy to disease recurrence, disease progression, initiation of salvage treatment, or death from any cause
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Up to 5 years after completion of radiotherapy
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Incidence of Acute Treatment-related Toxicity
기간: During treatment and up to 3 months after completion of radiotherapy
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Incidence of acute treatment-related toxicity during radiotherapy and at 1- and 3-month follow-up after treatment, assessed using CTCAE version 5.0.
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During treatment and up to 3 months after completion of radiotherapy
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Incidence of Late (Chronic) Treatment-related Toxicity
기간: From 6 months up to 5 years after completion of radiotherapy
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Incidence of late (chronic) treatment-related toxicity assessed at 6 and 12 months, and at 3 and 5 years after treatment using CTCAE version 5.0.
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From 6 months up to 5 years after completion of radiotherapy
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Quality of Life Assessed by EQ-5D-5L
기간: During treatment and up to 5 years after completion of radiotherapy
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Patient-reported quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) during treatment and at 1-, 3-, 6-, and 12-month, and 3- and 5-year follow-up.
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During treatment and up to 5 years after completion of radiotherapy
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공동 작업자 및 조사자
협력자
협력자
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
기타 연구 ID 번호
- Si 577/2569(IRB1)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
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미국 FDA 규제 기기 제품 연구
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