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

NCT07276360 | Recruiting Phase 2 DMC

• 5 other identifiers: U050D43TW009759HS5348ESMak-SOMREC-2023-775RG1125359
• Study Type: interventional
• Target: 278
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

Cervical cancer; Radiotherapy; Hypofractionation; Uganda

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events (AEs)

  It will be categorized into 5 grades. The Conchran-Mantel-Haenszel test will be used to compare differences in the grades of AEs between patients who will receive hypofractionated radiotherapy versus conventional fractionated radiotherapy by stratifying for HIV status. A p-value of \< 5% will be regarded as significant.

  Up to 90 days post-treatment

• Incidence of grade 3 or greater radiotherapy-related gastrointestinal or genitourinary AEs

  Will compare the proportion of patients between the hypofractionated radiotherapy and conventional fractionated radiotherapy using a risk difference approach, and the 95% confidence interval (CI) for the difference in proportion will be estimated using the Farrington-Manning test. Non-inferiority will be determined when the upper bound of a two-sided 95% CI is less than 10%.

  At 1 and 2 years post-treatment

• Local control (complete remission, stable disease, and partial response) rate

  Will be compared using means, medians, standard deviations, and ranges for continuous variables and frequencies and percentages for categorical variables. Differences in local control for each treatment group and the 95% CI will be calculated using the Chi-square test or Fisher's exact test. Data on tumor sizes that are normally distributed will be presented as means and standard deviations with 95% CI. The log-rank test will be used to compare the local control rates. The mean difference between groups will be calculated using an independent T-test for normally distributed data. Will compare the proportion between arms using a risk difference approach and the 95% CI, the difference in proportion will be estimated using the Farrington-Manning test. Non-inferiority will be determined when the upper bound of a two-sided 95% Confidence interval is less than 10%.

  At 1 and 2 years post-treatment

Secondary Outcomes (2)

• Cervical cancer-specific survival

  At 1 and 2 years post-treatment

• Progression-free survival (PFS)

  From randomization to the date of first recurrence or progression of disease or death, assessed up to 2 years

Other Outcomes (4)

• Squamous cell carcinoma antigen (SCC-Ag)

  At baseline, at 4 weeks post-treatment

• Association of SCC-Ag levels and PFS

  Up to 1 and 2 years post-treatment

• Health-related quality of life (costs of healthcare)

  Up to 2 years post-treatment

Study Arms (2)

Arm I (HFRT)

EXPERIMENTAL

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.

Radiation: Hypofractionated Radiation Therapy; Drug: Cisplatin; Radiation: High-Dose Rate Brachytherapy; Radiation: External Beam Radiotherapy Boost; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Other: Questionnaire and Physical Exam

Arm II (CFRT)

ACTIVE COMPARATOR

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.

Radiation: Conventional Fractionated Radiotherapy; Drug: Cisplatin; Radiation: High-Dose Rate Brachytherapy; Radiation: External Beam Radiotherapy Boost; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Other: Questionnaire and Physical Exam

Interventions

Hypofractionated Radiation Therapy 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).

Also known as: Hypofractionated, hypofractionated radiotherapy, Hypofractionation, Moderately Hypofractionated Radiotherapy

Arm I (HFRT)

Conventional Fractionated Radiotherapy RADIATION

Undergoing CFRT

Also known as: Normofractionated Radiotherapy, Conventionally Fractionated Radiotherapy

Arm II (CFRT)

Cisplatin DRUG

Undergoing Cisplatin

Also known as: CDDP, Abiplatin, Platinum

Arm I (HFRT); Arm II (CFRT)

High-Dose Rate Brachytherapy RADIATION

Undergoing HDR Brachytherapy

Also known as: Brachytherapy, HDR, HDR Brachytherapy, High dose brachytherapy

Arm I (HFRT); Arm II (CFRT)

External Beam Radiotherapy Boost RADIATION

Undergoing external beam radiotherapy boost

Also known as: Boost, EBRT Boost, Boost Radiotherapy, Radiotherapy Boost

Arm I (HFRT); Arm II (CFRT)

Computed Tomography PROCEDURE

Undergoing CT scan

Also known as: CAT scan, CAT, Planning CT scan, CT scan, Computed Axial Tomography, Computed Axial Tomography Scan

Arm I (HFRT); Arm II (CFRT)

Biospecimen Collection PROCEDURE

Undergoing blood sample collection

Also known as: Blood sample, Biological sample collection, Biospecimen collected, Specimen collection

Arm I (HFRT); Arm II (CFRT)

Questionnaire and Physical Exam OTHER

Ancillary Studies

Also known as: CRF, Questionnaire, Assessment, Physical Exam

Arm I (HFRT); Arm II (CFRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Uganda Cancer Institute: lead
• Varian Medical Systems: collaborator
• Fogarty International Center of the National Institute of Health: collaborator

Study Sites (1)

Uganda Cancer Institute

Kampala, Kampala, 256, Uganda

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Radiation Dose Hypofractionation; Cisplatin; Platinum; Brachytherapy; Blood Specimen Collection; Specimen Handling; Surveys and Questionnaires; Restraint, Physical

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Behavior Control; Immobilization

Study Officials

• Solomon Kibudde, MBChB, MMed.

  Uganda Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Solomon Kibudde, MBChB, MMed.

CONTACT

+256773004608; solomon.kibudde@uci.or.ug

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 30, 2025
• First Posted: December 11, 2025
• Study Start: March 11, 2026
• Primary Completion (Estimated): January 2, 2028
• Study Completion (Estimated): January 2, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

UG (1)