Hypofractionated Chemoradiotherapy for Cervical Cancer (HYPOCx)

HYPOfractionated Whole Pelvic Concurrent Chemoradiotherapy in Cervical Cancer (HYPOCx Trial): A Phase III Randomized Controlled Trial

Cervical cancer remains a major health problem in Thailand and other lowand middle-income countries. The current standard treatment for locally advanced cervical cancer consists of conventionally fractionated external beam radiotherapy delivered over 5-7 weeks with concurrent chemotherapy, followed by brachytherapy. This prolonged treatment schedule requires frequent hospital visits and may limit access to care. Hypofractionated radiotherapy delivers a higher dose of radiation per treatment session while maintaining a comparable total radiation dose, thereby reducing the overall treatment duration. Preliminary studies suggest that hypofractionated chemoradiotherapy using modern radiotherapy techniques may provide similar disease control and acceptable toxicity compared with conventional treatment, while improving treatment convenience and reducing healthcare burden. This multicenter phase III randomized controlled trial aims to compare hypofractionated whole pelvic concurrent chemoradiotherapy with conventional chemoradiotherapy in patients with early-stage node-positive and locally advanced cervical cancer. The study will evaluate nodal control and overall survival, as well as tumor response, treatment-related toxicities, quality of life, and cost-effectiveness.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervival Cancer
• Intervention / Treatment: Radiation: Conventional Chemoradiotherapy; Drug: Concurrent chemotherapy; Radiation: Hypofractionated Chemoradiotherapy

Detailed Description

Cervical cancer remains one of the leading causes of cancer-related morbidity and mortality among women in Thailand and other low- and middle-income countries. Although improvements in cervical cancer screening programs and human papillomavirus (HPV) vaccination have reduced disease incidence, a substantial proportion of patients continue to present with locally advanced disease requiring definitive chemoradiotherapy. The current standard treatment for locally advanced cervical cancer consists of conventionally fractionated external beam radiotherapy (45-50.4 Gy delivered in 25-28 fractions) administered concurrently with platinum-based chemotherapy, followed by image-guided brachytherapy. This treatment approach requires daily hospital visits over approximately 5-7 weeks and may contribute to treatment burden, limited access to radiotherapy services, and prolonged overall treatment time. Hypofractionated radiotherapy shortens treatment duration by delivering a higher dose per fraction while maintaining an equivalent biologically effective dose. This strategy has become an accepted standard of care in several malignancies, including breast, prostate, and rectal cancers. Emerging evidence suggests that hypofractionated chemoradiotherapy for cervical cancer using modern techniques such as intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT), combined with image-guided adaptive brachytherapy, provides acceptable toxicity profiles and promising disease control outcomes. The phase II HYPOCx-iRex trial demonstrated comparable gastrointestinal toxicity and encouraging oncologic outcomes between hypofractionated and conventional chemoradiotherapy regimens. Additional prospective studies have reported favorable response rates, disease control, and acceptable treatmentrelated toxicities with hypofractionated approaches. Moreover, hypofractionated treatment may improve healthcare efficiency and reduce societal costs by decreasing the number of treatment visits. This multicenter phase III randomized controlled trial will compare hypofractionated whole pelvic concurrent chemoradiotherapy with conventional chemoradiotherapy in patients with early-stage node-positive and locally advanced cervical cancer. Participants will be randomized to receive either hypofractionated external beam radiotherapy or conventional fractionation, both delivered using IMRT/VMAT techniques with concurrent chemotherapy and image-guided adaptive brachytherapy. The primary outcomes are nodal control and overall survival. Secondary outcomes include tumor response, local and regional disease control, eventfree survival, treatment-related toxicities, quality of life, and cost-effectiveness.

The findings from this study are expected to provide high-level evidence regarding the efficacy, safety, and economic value of hypofractionated chemoradiotherapy and may support broader implementation of this treatment strategy in resource-constrained settings.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tissana Prasartseree, MD; Phone Number: 66625246101; Email: tissana.p@gmail.com
• Study Contact Backup: Name: Pittaya Dankulchai, MD; Phone Number: 66966233606; Email: pittaya.dan@mahidol.ac.th

Study Locations

• Thailand
  • Bangkok
    • Bangkok Noi, Bangkok, Thailand, 10700
      • Siriraj Hospital
      • Contact: Tissana Prasartseree, MD; Phone Number: 66625246101; Email: tissana.p@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Cancer of the uterine cervix considered suitable for curative treatment with definitive radio-(chemo)therapy including imaged-guided BT
2. Positive biopsy showing squamous-cell carcinoma, adenocarcinoma, or adeno-squamous cell carcinoma of the uterine cervix
3. Locally advanced staging according to FIGO 2018 and TNM guidelines (Stage IA1-IVA)
4. MRI of the pelvis at diagnosis is performed
5. MRI, CT, or PET-CT of the retroperitoneal space and abdomen at diagnosis is performed
6. MRI with the applicator in place at the time of (first) BT will be performed
7. GFR ≥ 50 mL/min
8. Patient informed consent

Exclusion Criteria:

1. Other primary malignancies except carcinoma in situ of the cervix and basal cell carcinoma of the skin
2. Small cell neuroendocrine cancer, melanoma and other rare cancers in the cervix
3. Metastatic disease beyond intervertebral disc L2/3 level
4. Previous pelvic or abdominal radiotherapy
5. Previous total or subtotal hysterectomy
6. Combination of preoperative radiotherapy with surgery
7. Patients receiving BT only
8. Patients receiving EBRT only
9. Patients receiving neo-adjuvant chemotherapy or other forms of antineoplastic treatment apart from weekly concomitant cisplatin (40 mg/m2).
10. Contra-indications to MRI
11. Contra-indications to BT

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
Active Comparator: 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.	Radiation: Conventional Chemoradiotherapy; 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.; Drug: Concurrent chemotherapy; 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.
Experimental: 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.	Drug: Concurrent chemotherapy; 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.; Radiation: Hypofractionated Chemoradiotherapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nodal Recurrence-free Survival	Time from completion of radiotherapy to the first occurrence of nodal recurrence	Up to 5 years after completion of radiotherapy
Overall Survival (OS)	Time from completion of radiotherapy to death from any cause.	Up to 5 years after completion of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Recurrence-free Survival	Time from completion of radiotherapy to local tumor recurrence.	At 3 and 5 years after completion of radiotherapy
Incremental Cost-effectiveness Ratio per Quality-adjusted Life Year Between Hypofractionated and Conventional Radiotherapy	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.	During treatment and follow-up up to 5 years after completion of radiotherapy.
Tumor Response Rate	Tumor response rate assessed after external beam radiotherapy and at 3-, 6-, and 12-month follow-up after treatment.	Up to 12 months after completion of radiotherapy
Pelvic Recurrence-free Survival	Time from completion of radiotherapy to pelvic recurrence.	At 3 and 5 years after completion of radiotherapy
Para-aortic Recurrence-free Survival	Time from completion of radiotherapy to para-aortic recurrence.	At 3 and 5 years after completion of radiotherapy
Locoregional Recurrence-free Survival	Time from completion of radiotherapy to local, pelvic, or para-aortic recurrence.	At 3 and 5 years after completion of radiotherapy
Distant Metastasis-free Survival	Time from completion of radiotherapy to distant metastasis.	At 3 and 5 years after completion of radiotherapy
Event-free Survival	Time from completion of radiotherapy to disease recurrence, disease progression, initiation of salvage treatment, or death from any cause	Up to 5 years after completion of radiotherapy
Incidence of Acute Treatment-related Toxicity	Incidence of acute treatment-related toxicity during radiotherapy and at 1- and 3-month follow-up after treatment, assessed using CTCAE version 5.0.	During treatment and up to 3 months after completion of radiotherapy
Incidence of Late (Chronic) Treatment-related Toxicity	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.	From 6 months up to 5 years after completion of radiotherapy
Quality of Life Assessed by EQ-5D-5L	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. The EQ-5D-5L descriptive system assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/ depression across 5 levels of severity. The EQ Visual Analog Scale (EQ-VAS) ranges from 0 to 100, with higher scores indicating better perceived health status.	During treatment and up to 5 years after completion of radiotherapy

Collaborators and Investigators

• Sponsor: Mahidol University
• Collaborators: Prince of Songkla University; Chiang Mai University; Chulabhorn Hospital; Siriraj Hospital; Ratchaburi Hospital; Tha Chalom Hospital; Lopburi Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2033

Study Registration Dates

• First Submitted: July 12, 2026
• First Submitted That Met QC Criteria: July 12, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 16, 2026
• Last Update Submitted That Met QC Criteria: July 12, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Cervical Cancer; Brachytherapy; Hypofractionated Radiotherapy; Chemoradiotherapy; Conventional Radiotherapy; Whole Pelvic 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: Si 577/2569(IRB1)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No