Hypofractionated Radiochemotherapy

Uterine Cervix Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06331468
• Other study ID #: MCC-23-GYN-10
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2024
• Est. completion date: August 1, 2028

Study information

• Verified date: March 2024
• Source: University of Kentucky
• Contact: Yvonne Taul, RN
• Phone: 859-323-2354
• Email: yvonne.taul[@]uky.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: August 1, 2028
• Est. primary completion date: August 1, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 120 Years

Eligibility

Inclusion Criteria:

• Untreated, pathologically or cytologically-confirmed diagnosis of FIGO Stage IB3, II, or IIIA-IIIC1 bulky ( = 6cm) 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

Related Conditions & MeSH terms

• Uterine Cervical Neoplasms
• Uterine Cervix Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Markey Cancer Center	Lexington	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Denise Fabian

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	Treatment Tolerability	Assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0)	up to 2 years