A phase II multi-center, open-label, randomized, parallel-group, superiority study to compare the acute toxicity of Hypofractionated dOse Painted External radiotherapy versus conventional external radiotherapy in patients with carcinoma cervix stage I - IIB. (HOPE)

Introduction

The HOPE trial is a Phase II, multi-center, open-label, randomized, parallel-group superiority study comparing acute toxicity of hypofractionated dose-painted external radiotherapy versus conventional external radiotherapy in patients with carcinoma cervix stages I-IIB (FIGO 2018). The trial will be conducted in India with enrollment commencing July 2026.

Methods and analysis

A total of 300 patients will be randomized in a 1:1 ratio to experimental or control arms. The experimental arm employs dose-painted interval-compressed concurrent chemoradiation utilizing volumetric modulated arc therapy (VMAT), delivering 42.5 Gy in 20 fractions over 4 weeks to the primary clinical target volume and 36 Gy in 20 fractions over 4 weeks to elective pelvic nodal volumes (external iliac, internal iliac, presacral, and common iliac). Concurrent chemotherapy consists of weekly cisplatin 50 mg/m². The control arm delivers conventional concurrent chemoradiation with VMAT at 45 Gy in 25 fractions over 5 weeks to both primary and elective volumes, with weekly cisplatin 40 mg/m². Both arms receive image-guided brachytherapy to achieve a total equivalent dose of at least 80 Gy₁₀ to the high-risk clinical target volume.

The primary endpoint is the proportion of patients experiencing grade ≥2 gastrointestinal toxicity (diarrhea, vomiting, nausea) per CTCAE 6.0 criteria. Secondary endpoints include three-year disease-free survival, quality of life, and late toxicity.

Ethics and dissemination

The study has been approved by the institutional review board of Tata Medical center. Additional centers will have independent IRB approval after adequate extramural funding has been secured. The results will be disseminated in peer reviewed publications in journals and presented in academic meetings. The study will be conducted as per the applicable laws and regulations of the Indian regulator authorities.

Registration details

Indian Clinical Trial Registry (CTRI) CTRI/2026/05/111292

Strengths and Limitations

• First trial of its kind evaluating simultaneous dose de-escalation with hypofractionation with adequate sample size to evaluate impact of toxicity reduction due to bowel and bone marrow dose reduction

• Cumulative dose of cisplatin as well as therapeutic dose fractionation (1.8 Gy) maintained - pure dose de-escalation being evaluated.

• Rigorous multi-step multi-center quality assurance planned

• Limited to accrual in Indian patients.

• Requirement of Intensity Modulated radiotherapy for external beam radiotherapy delivery.