Clinical trial NCT06509724: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Uterine Cervical Neoplasms
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2024-07-19
Enrollment: 248
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Local control rate for the radiation treatment area
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 5 years
measure: Disease-free survival (DFS)
timeFrame: Up to 5 years
measure: Acute Toxicity Profile
timeFrame: During treatment and up to 3 months post-treatment
measure: Late Toxicity Profile
timeFrame: From 3 months post-treatment up to 5 years
measure: Quality of life (QoL)
timeFrame: Baseline, end of treatment, 6 months post-treatment, and annually up to 5 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
Study officials:
References: