Hypofractionated Radiotherapy for the Treatment of Locally Advanced Cervical Cancer in Uganda

NCT ID: NCT07276360

Last Updated: 2025-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

278 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-03

Study Completion Date

2029-01-02

Brief Summary

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This phase II trial compares the effect of hypofractionated radiotherapy (HFRT) to conventional fractionated radiotherapy (CFRT) when given in combination with cisplatin and brachytherapy in patients with stage IB3, II, or III cervical cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. CFRT delivers the total dose of radiation over the amount of time according to standard practice. HFRT delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. HFRT shortens treatment duration and may reduce costs and may improve the completion rates. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. HFRT may be safe, tolerable, and/or as effective as CFRT when given in combination with cisplatin and brachytherapy in treating patients with stage IB3, II or III cervical cancer.

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine the safety, and efficacy of hypofractionated radiotherapy (40 Gy in 16 fractions) compared to conventional fractionated radiotherapy (45 Gy in 25 fractions) in women with locally advanced cervical cancer in Uganda.

SPECIFIC OBJECTIVES:

I. To compare the incidence of grade 3+ gastrointestinal and genitourinary toxicity at 1- and 2-years post-treatment with hypofractionated radiotherapy (40 Gy in 16 fractions) and conventional fractionated radiotherapy (45 Gy in 25 fractions) in women with cervical cancer in Uganda.

II. To evaluate and compare local control and cervical cancer-specific survival rates at 1 and 2 year after hypofractionated radiotherapy (40 Gy in 16 fractions) versus conventional radiotherapy (45 Gy in 25 fractions).

III. To determine the association between stage-adjusted mean squamous cell carcinoma antigen (SCC-Ag) at 1-month post-treatment with the progression-free survival at 1- and 2- years post-treatment with hypofractionated radiotherapy (40 Gy in 16 fractions) or conventionally fractionated radiotherapy (45 Gy in 25 fractions).

IV. To compare the costs of healthcare to patients with cervical cancer treated with hypofractionated radiotherapy (40 Gy in 16 fractions) versus conventional fractionated radiotherapy (45 Gy in 25 fractions).

V. To evaluate patient-reported outcomes and quality of life in patients with cervical cancer treated with hypofractionated radiotherapy (40 Gy in 16 fractions) versus conventional fractionated radiotherapy (45 Gy in 25 fractions).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (INTERVENTION): Patients undergo HFRT once daily (QD), Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour once weekly (QW) during radiation therapy. Starting by week 4, patients may also undergo high dose rate (HDR) brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo computed tomography (CT) and blood sample collection throughout the study.

ARM II (CONTROL): Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30, 90, 180, 360, 540, and 720 days.

Conditions

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Cervical Cancer Cervix Cancer Cervical Adenocarcinoma Cervical Small Cell Carcinoma Cervical Adenosquamous Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This is an open-label phase II randomized non-inferiority trial with a parallel group design. One hundred and twenty participants will be randomized 1:1 into two arms - conventional fractionated radiotherapy or hypofractionated radiotherapy.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

This study does not provide for blinding of participants or providers due to the significant differences between the study intervention and control in terms of the duration of treatment, three weeks compared to five weeks of external beam radiotherapy. However, information bias will be minimized by ensuring that data collectors (research staff) are not directly involved in the delivery of treatment for study patients

Study Groups

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Arm I (HFRT)

Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.

Group Type EXPERIMENTAL

Hypofractionated Radiation Therapy

Intervention Type RADIATION

Undergoing HFRT - The prescription dose will be 40 Gy in 16 fractions (2.5 Gy/fraction) to the entire pelvis, with concurrent integrated nodal boost at 3.0 Gy per fraction (48 Gy) to involved (positive) pelvic nodes, delivered once a day, Monday through Friday, 5 fractions per week, using volumetric modulated arc therapy (VMAT).

Cisplatin

Intervention Type DRUG

Undergoing Cisplatin

High-Dose Rate Brachytherapy

Intervention Type RADIATION

Undergoing HDR Brachytherapy

External Beam Radiotherapy Boost

Intervention Type RADIATION

Undergoing external beam radiotherapy boost

Computed Tomography

Intervention Type PROCEDURE

Undergoing CT scan

Biospecimen Collection

Intervention Type PROCEDURE

Undergoing blood sample collection

Questionnaire and Physical Exam

Intervention Type OTHER

Ancillary Studies

Arm II (CFRT)

Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.

Group Type ACTIVE_COMPARATOR

Conventional Fractionated Radiotherapy

Intervention Type RADIATION

Undergoing CFRT

Cisplatin

Intervention Type DRUG

Undergoing Cisplatin

High-Dose Rate Brachytherapy

Intervention Type RADIATION

Undergoing HDR Brachytherapy

External Beam Radiotherapy Boost

Intervention Type RADIATION

Undergoing external beam radiotherapy boost

Computed Tomography

Intervention Type PROCEDURE

Undergoing CT scan

Biospecimen Collection

Intervention Type PROCEDURE

Undergoing blood sample collection

Questionnaire and Physical Exam

Intervention Type OTHER

Ancillary Studies

Interventions

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Hypofractionated Radiation Therapy

Undergoing HFRT - The prescription dose will be 40 Gy in 16 fractions (2.5 Gy/fraction) to the entire pelvis, with concurrent integrated nodal boost at 3.0 Gy per fraction (48 Gy) to involved (positive) pelvic nodes, delivered once a day, Monday through Friday, 5 fractions per week, using volumetric modulated arc therapy (VMAT).

Intervention Type RADIATION

Conventional Fractionated Radiotherapy

Undergoing CFRT

Intervention Type RADIATION

Cisplatin

Undergoing Cisplatin

Intervention Type DRUG

High-Dose Rate Brachytherapy

Undergoing HDR Brachytherapy

Intervention Type RADIATION

External Beam Radiotherapy Boost

Undergoing external beam radiotherapy boost

Intervention Type RADIATION

Computed Tomography

Undergoing CT scan

Intervention Type PROCEDURE

Biospecimen Collection

Undergoing blood sample collection

Intervention Type PROCEDURE

Questionnaire and Physical Exam

Ancillary Studies

Intervention Type OTHER

Other Intervention Names

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Hypofractionated hypofractionated radiotherapy Hypofractionation Moderately Hypofractionated Radiotherapy Normofractionated Radiotherapy Conventionally Fractionated Radiotherapy CDDP Abiplatin Platinum Brachytherapy HDR HDR Brachytherapy High dose brachytherapy Boost EBRT Boost Boost Radiotherapy Radiotherapy Boost CAT scan CAT Planning CT scan CT scan Computed Axial Tomography Computed Axial Tomography Scan Blood sample Biological sample collection Biospecimen collected Specimen collection CRF Questionnaire Assessment Physical Exam

Eligibility Criteria

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Inclusion Criteria

* Females aged 18 years or older
* Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the uterine cervix without prior treatment
* Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3, IIA, IIB, IIIA, IIIB, or IIIC
* Able to provide written informed consent in English, Luganda, Runyankole, or Lango
* Willing to attend post-treatment follow-up for up to 12 months
* Fit for concurrent chemotherapy with cisplatin
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2
* Absolute neutrophil count ≥ 1,500 cells/mm\^3 (1.5 x 10\^9/L)
* Platelets ≥ 100,000 cells/mm\^3 (100 x 10\^9/L)
* Hemoglobin ≥ 9.0 g/dL
* Leukocyte count ≥ 4,000 cells/mm\^3 (4.0 x 10\^9/L)
* Creatinine clearance \> 60 mL/mins, calculated using the Cockcroft-gault equation for women
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 times the upper limit of normal (ULN)
* Total bilirubin \< 2 x ULN unless attributed to the use of antiretroviral therapy (ART)
* HIV-positive participants must be on a stable ART regimen for at least 6 weeks prior to enrollment

Exclusion Criteria

* Prior hysterectomy. Women with previous total or subtotal hysterectomy have no cervix, and hence the anatomical changes have an impact on the radiotherapy field, and dose prescriptions because they tend to have a higher risk for bowel toxicity from pelvic radiotherapy. Therefore, these women will be excluded due to the likely impact on the results of our study intervention
* Clinical and/or radiological evidence of distant metastases
* Prior pelvic or abdominal radiotherapy
* Presence of bilateral hip prosthesis that could interfere with radiotherapy treatment
* History of inflammatory bowel disease or any other condition that could complicate radiotherapy treatment
* Participants who are pregnant at the time of enrollment. Pregnant women have a potential risk of radiation exposure to developing fetus, which may result in fetal malformations, growth retardation, or even fatal death. Secondly, their physiological changes alter the pharmacokinetics and pharmacodynamics of concurrent chemotherapy. Therefore, to protect the health of the mother and the unborn child, pregnant women will be excluded from the study. Patients who are found to be pregnant after enrollment will have the study procedures terminated
* Concurrent untreated invasive malignancy
* Uncontrolled concurrent medical/psychiatric diagnosis that would limit compliance with study requirements
* Uncontrolled HIV infection, especially HIV viral load \> 2,000 copies/mL
* Participants with CD4 counts \< 200 cells/mm\^3
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Uganda Cancer Institute

OTHER

Sponsor Role lead

Varian Medical Systems

INDUSTRY

Sponsor Role collaborator

Fogarty International Center of the National Institute of Health

NIH

Sponsor Role collaborator

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Solomon Kibudde, MBChB, MMed.

Role: PRINCIPAL_INVESTIGATOR

Uganda Cancer Institute

Locations

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Uganda Cancer Institute

Kampala, Kampala, Uganda

Site Status

Countries

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Uganda

Central Contacts

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Solomon Kibudde, MBChB, MMed.

Role: CONTACT

+256773004608

Facility Contacts

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Solomon Kibudde, MBChB, MMed

Role: primary

0773004608

Other Identifiers

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D43TW009759

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HS5348ES

Identifier Type: OTHER

Identifier Source: secondary_id

Mak-SOMREC-2023-775

Identifier Type: OTHER

Identifier Source: secondary_id

RG1125359

Identifier Type: OTHER

Identifier Source: secondary_id

U050

Identifier Type: -

Identifier Source: org_study_id

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