Comparison of Conventional and Hypofractionated IMRT in High-Risk Cervical Cancer Post-Radical Hysterectomy

Official title

Postoperative Conventional Versus Hypofractionated Intensity-modulated Radiation Therapy With Concurrent Chemotherapy in Cervical Cancer: A Prospective Multicenter Randomized Phase III Trial (POHIM_P3 Trial)

Overview

Radical hysterectomy and radiation therapy are standard treatments for cervical cancer. However, there are no reported studies on the frequency of side effects and treatment outcomes when hypofractionated radiation therapy and intensity modulated radiation therapy(IMRT) are used during radiation therapy. Hypofractionated radiation therapy increases the daily dose and reduces the number of treatment sessions, which may increase the risk of side effects, but its safety has been confirmed in some cases of early cervical cancer and endometrial cancer. Additionally, applying IMRT, a technique designed to protect normal tissue, during concurrent chemoradiotherapy has shown positive results in reducing the incidence of acute side effects. Investigators previously demonstrated that combining hypofractionated IMRT with chemotherapy for high-risk postoperative cervical cancer patients resulted in high survival rates and low toxicity in a phase 2 exploratory study. Base on this result, this study aimed to compare the efficacy and safety of conventional fractionated radiation therapy and hypofractionated radiation therapy.

Detailed description

* This phase 3 multicenter randomized controlled trial evaluates two radiation therapy regiments in high-risk cervical cancer patients who have undergone radical hysterectomy. Participants are randomly assigned in a 1:1 ratio to receive either conventional fractionated IMRT(Intensity modulated radiation therapy) or hypo fractionated IMRT, both in combination with concurrent chemotherapy. * The conventional fractionation group receives 1.8-2.0 Gy per session for a total of 25-28 sessions (total 40-50.4 Gy) with weekly chemotherapy (total 5-6 sessions). The hypofractionation group receives 2.5 Gy per session for a total of 16 sessions (total 40 Gy) with weekly chemotherapy (total 3 sessions). Brachytherapy is allowed in both group. * Stratification factors for randomization include lymph node metastasis status and adenocarcinoma vs. non-adenocarcinoma. Blocked randomization will be used. The study aims to assess local control rates, overall, survival, disease-free survival, and acute and late toxicity profiles.

Interventions

• Radiation Conventional Fractionated IMRT
  * Dose: 1.8-2.0 Gy per session, total 25-28 sessions (40-50.4Gy) * Chemotherapy: Weekly, total 5-6 sessions
• Radiation Hypofractionated IMRT
  * Dose: 2.5 Gy per session, total 16 sessions (40Gy) * Chemotherapy: Weekly, total 3 sessions

Primary outcome measures

• Local control rate for the radiation treatment area [Time frame: Up to 3 years]

Secondary outcome measures (5)

• Overall survival (OS) [Time frame: Up to 5 years]
• Disease-free survival (DFS) [Time frame: Up to 5 years]
• Acute Toxicity Profile [Time frame: During treatment and up to 3 months post-treatment]
• Late Toxicity Profile [Time frame: From 3 months post-treatment up to 5 years]
• Quality of life (QoL) [Time frame: Baseline, end of treatment, 6 months post-treatment, and annually up to 5 years]

Eligibility criteria

Inclusion criteria

• Patients diagnosed histologically with cervical cancer
• Patients diagnosed histologically with Squamous cell carcinoma, Adenocarcinoma, or Adenosquamous carcinoma
• Patients who have undergone radical hysterectomy and pelvic lymphadenectomy
• Patients who meet the indication for radiotherapy in postoperative pathological examination (at least on of the following):

A. Pelvic lymph node metastasis B. Parametrial involvement C. Positive surgical margins

• Adult aged 20 to 75 years
• Patients with an ECOG 0-1 within 1 week prior to study participation
• Maintained bone marrow function: granulocyte ≥1.0 x 103/µl, platelets ≥30 x 103/µl, hemoglobin ≥9.5 g/dl
• Maintained renal and liver function (Creatinine <2.0 mg/dL, Bilirubin < 1.5 mg/dl)
• Patients who have voluntarily signed the consent form

Exclusion criteria

• Patients with distance metastasis (including ovarian and para-aortic lymph node metastasis)
• Patients who have previously received radiotherapy to the pelvic area
• Patients who have undergone radical hysterectomy more than 3 months prior
• Patients with untreated serious acute illnesses (e.g., stroke, cerebral infarction, myocardial infarction) other than cervical cancer
• Patients who received neoadjuvant chemotherapy before surgery
• Patients who will not receive concurrent chemotherapy during radiotherapy
• Patients with a history of another cancer diagnosis within the past 5 years, except for thyroid cancer, skin cancer, or carcinoma in suit

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Samsung Medical Center — Seoul

Publications

• Cho WK, Park W, Lee JH, Kang HC, Yoon M, Eom KY, Kim YS, Park S, Kim YS, Kim YJ, Choi E, Kim DY. Postoperative conventional versus hypofractionated intensity-modulated radiation therapy with concurrent chemotherapy in cervical cancer: a prospective multicenter randomized phase III trial (POHIM_P3 trial). J Gynecol Oncol. 2026 Jan;37(1):e4. doi: 10.3802/jgo.2026.37.e4. Epub 2025 Jul 4. PMID 40676909

Identifiers

NCT: NCT06509724 · SMC 2024-04-058 · KROG 24-05

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗