Hypofractionated Radiochemotherapy

Phase II Trial of Hypofractionated Radiochemotherapy for Women With Metastatic or Bulky Uterine Cervix Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Uterine Cervix Cancer
• Intervention / Treatment: Drug: Cisplatin; Radiation: intensity modulated radiation therapy (IMRT); Radiation: high-dose-rate (HDR) brachytherapy

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yvonne Taul, RN; Phone Number: 859-323-2354; Email: yvonne.taul@uky.edu
• Study Contact Backup: Name: Denise Fabian, MD

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • Markey Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Untreated, pathologically or cytologically-confirmed diagnosis of FIGO Stage IB3, II, or IIIA-IIIC1 bulky ( ≥ 6cm) or Stage IVA or Stage IVB (FIGO 2018) squamous, adenosquamous, or adenocarcinoma of the uterine cervix with limited metastatic burden (not requiring urgent systemic therapy).
• Adequate organ and marrow function
• Gynecologic Oncology Group performance status of 0, 1, or 2
• Patient agrees to use two forms of birth control if they are of child-bearing potential
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Presence of another concurrent active invasive malignancy
• Prior invasive malignancy diagnosed within the last three years, with the following two exceptions: [a] non-melanoma skin cancer and/or [b] prior in situ carcinoma of the cervix
• Receipt of prior pelvic radiotherapy for any reason that would contribute radiation dose that would exceed tolerance of normal tissues, at the discretion of the treating physician
• Currently receiving any other investigational agent(s) for the treatment of cancer
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Cisplatin or other agents used in study
• Presence of uncontrolled intercurrent illness as determined by the treating physician
• pregnant or lactating
• Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cisplatin with concurrent Intensity Modulated Radiotherapy and Brachytherapy; Cisplatin two (2) one-time weekly intravenous infusions at 40 mg/m2 (70mg maximum) IMRT once daily, four fractions per week for 2 weeks 4.56 Gy x 8 fractions High dose rate Brachytherapy twice per week with a 2-day break in between sessions for a total of four brachytherapy treatments. The dose is 7 Gy x 4 fractions

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.; Other Names: Platinol; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI assessed rate of complete response	MRI-assessed rates of complete response as estimated by the number of CRs (complete response per RECIST v1.1) divided by the total number of evaluable subjects	1 month post treatment (day 60)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI assessed rate of complete response	The proportion of complete response will be assessed at 3-mos post-treatment completion, i.e., Day 120, as estimated by the number of CRs (complete response per RECIST v1.1) divided by the total number of evaluable subjects.	3 months post treatment (day 120)
progression-free survival (PFS)	Progression-free survival (PFS) is calculated from the date of treatment start (week 1, day 1) to the date of initial disease progression or to the date of death or to 2-years post-treatment initiation, whichever occurs first.	up to 2 years
overall survival (OS)	Overall Survival is calculated from the date of treatment start until date of death or up to 2-years post-treatment initiation, whichever occurs first.	up to 2 years
Treatment Completion	reported as a proportion of subjects who complete entire prescribed course of the treatment based on the treatment compliance for Radiotherapy and for Cisplatin	up to 32 days
Treatment Tolerability	Assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0)	up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in levels of uterine cervix cancer circulating tumor cells	A total of 15mL of peripheral venous blood will be collected for Circulating tumor cells (CTC). Counts will be reported as means with standard deviations in tabular format	pre-treatment; 1-month post-treatment completion (Day 60); and 3-mos post-treatment completion (Day 120)

Collaborators and Investigators

• Sponsor: Denise Fabian
• Investigators: Principal Investigator: Denise Fabian, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: March 19, 2024
• First Posted (Actual): March 26, 2024

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Cisplatin; Uterine Neoplasm
• 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 Cervical Neoplasms; Uterine Neoplasms; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Cisplatin; Radiotherapy, Intensity-Modulated; Brachytherapy
• Other Study ID Numbers: MCC-23-GYN-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No