Hypofractionated Radiochemotherapy

Summary

The goal of this clinical trial is to investigate the use of hypofractionated radiation (delivery of fewer but larger doses of radiation) with concurrent chemotherapy for women with metastatic of bulky uterine cervix cancer. The main questions it aims to answer are:

* What is the MRI-assessed rate of response at 1-month and 3-months post-treatment?
* What is the safety and tolerability of cisplatin-based hypofractionated pelvic Intensity Modulated Radiation Therapy (IMRT) followed by brachytherapy?
* What is the median progression-free survival and overall survival at 1 and 2 years for patients who undergo cisplatin-based hypofractionated pelvic IMRT?
* What is the proportion of patients who complete the treatment in prescribed timeframe?
* What the levels of cervix cancer circulating tumor cells pretherapy and after treatment?

To confirm eligibility, within four weeks prior to study enrollment, all patients will undergo the following:

* Complete history and physical exam, GOG performance status evaluation
* Standard of care scans, which include staging CTs and/or PET scans, and MRI to verify eligibility and appropriate stage of disease. Blood tests will be done to check various organ functions.

Treatment will be administered on an outpatient basis.

The main difference between the proposed regimen in the trial and standard of care is as follows:

1. The trial has a shortened course of EBRT. Standard of care utilizes 25 treatments, also known as "fractions" of EBRT, while the trial utilizes 8 fractions of EBRT. An equivalent "biological effective dose" is achieved by increasing the radiation dose per fraction.
2. The concurrent cisplatin dosing is shortened from 5-6 cycles of cisplatin to 2 cycles of cisplatin. The dose of cisplatin is 40 mg/m2.

This protocol requires photon IMRT technique followed by high dose rate (HDR) brachytherapy. The therapies use focused energy beams to kill cancer cells. Radiation therapy must be completed within 30 days +/- 2 days of initiation. Computed tomography simulation with the patient in a head-first laying on back-supine position is required. MRI-guided treatment planning and image guidance during treatment for motion management will be used.

IMRT will be given once daily Monday-Thursday, four fractions per week. The high-dose-rate (HDR) brachytherapy following institutional protocol. Brachytherapy will be delivered twice per week with a 2-day break in between sessions. A total of four brachytherapy treatments will be delivered.

After active therapy is completed, treatment-related toxicity will be assessed at the 1-month post-treatment completion visit and again at the 3-month post-treatment completion. Patients removed from the study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event(s).

Routine MRI imaging to assess treatment response to radiotherapy is conducted at Day 15. Treatment response to radiotherapy followed by brachytherapy will be assessed at the 1- month and 3-months post-treatment completion.

Following the 3-months post-treatment completion, study participants will be followed for disease progression and survival status until Year 2 post-treatment initiation. NOTE: Cervical cancer patients are routinely followed (clinical surveillance) every 3-months during the first two years post-treatment.

Conditions

• Uterine Cervix Cancer

Interventions

DRUG

Cisplatin

A total of two IV infusions of cisplatin will be administered on Day 1 and again on Day 8 +/- 1 day. Cisplatin starting dose is 40 mg/m2. Dose reduction is allowed (30 mg/m2) as needed for management of toxicities.

RADIATION

intensity modulated radiation therapy (IMRT)

given once daily Monday-Thursday, four fractions per week for 2 weeks. The radiation dose is 4.56 Gy x 8 fractions.

RADIATION

high-dose-rate (HDR) brachytherapy

administered 2x weekly (allow at least 72-hours window between sessions); weekdays only for 2 weeks. The radiation dose is 7 Gy x 4 fractions.

Sponsors & Collaborators

• Denise Fabian

  lead OTHER

Principal Investigators

• Denise Fabian, MD · University of Kentucky

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-06-26

Primary Completion

2026-07-01

Completion

2028-07-01

FDA Drug

Yes

Countries

• United States

Study Locations