Short-course (hypofractionated) versus standard radiotherapy with cisplatin and brachytherapy for locally advanced cervical cancer in Uganda

Phase II Randomized Non-Inferiority Trial of Hypofractionated Radiotherapy for Locally Advanced Cervical Cancer in Uganda

This trial tests whether a shorter, higher-dose radiotherapy schedule plus cisplatin and brachytherapy works as well and causes no more serious side effects than the usual longer schedule for women in Uganda with stage IB3–IIIC cervical cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 278 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Uganda Cancer Institute (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Kampala, Kampala)
• Trial ID: NCT07276360 on ClinicalTrials.gov

What this trial studies

This phase II comparison gives women with locally advanced cervical cancer either hypofractionated external beam radiotherapy (40 Gy in 16 fractions) or conventional external beam radiotherapy (45 Gy in 25 fractions), both delivered with concurrent cisplatin and followed by high‑dose‑rate brachytherapy. Key outcomes include grade 3 or higher gastrointestinal and genitourinary toxicity at 1 and 2 years, local control, cervical cancer–specific survival, changes in SCC‑Ag, patient‑reported quality of life, and out‑of‑pocket costs. Patients are followed for clinical and patient‑reported outcomes up to two years after treatment to compare safety, tumor control, and economic impact. The trial is conducted at the Uganda Cancer Institute in Kampala with the goal of shortening treatment time and improving completion rates in a low‑resource setting.

Who should consider this trial

Good fit: Women aged 18 or older with untreated, histologically confirmed squamous cell, adenosquamous, or adenocarcinoma of the cervix at FIGO 2018 stage IB3–IIIC who are fit for concurrent cisplatin, have ECOG performance status ≤2, and meet basic laboratory and renal function criteria are the intended participants.

Not a fit: Patients with histologies excluded by the entry criteria, prior pelvic radiotherapy or treatment for cervical cancer, poor kidney function, poor performance status, or who cannot travel to Kampala for daily radiotherapy are unlikely to benefit from joining this protocol.

Why it matters

Potential benefit: If successful, the shorter radiotherapy regimen could shorten treatment time, lower costs, improve the chance patients finish therapy, and provide similar tumor control with comparable or fewer serious side effects.

How similar studies have performed: Smaller and observational reports in resource‑limited settings have suggested short‑course external beam regimens can be safe and improve completion rates, but high‑quality randomized evidence in cervical cancer remains limited.

Eligibility criteria

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

Where this trial is running

Kampala, Kampala

• Uganda Cancer Institute — Kampala, Kampala, Uganda (RECRUITING)

Study contacts

• Principal investigator: Solomon Kibudde, MBChB, MMed. — Uganda Cancer Institute
• Study coordinator: Solomon Kibudde, MBChB, MMed.

Conditions: Cervical Cancer, Cervix Cancer, Cervical Adenocarcinoma, Cervical Small Cell Carcinoma, Cervical Adenosquamous Carcinoma, Cervical cancer, Radiotherapy, Hypofractionation