Accelerated Brachytherapy Forward Chemo Radiation Therapy (ABC-RT) for Locally-advanced Cervical Cancer

The standard treatment for locally advanced cervical cancer is well established as a combination of chemotherapy and radiation, typically over 25-28 daily fractions with the addition of a brachytherapy boost to the primary tumor. An important component to treatment efficacy is overall treatment time. Prolongation of overall treatment time has been shown to lead to worse local control and overall survival; thus, strategies to effectively deliver radiation efficiently is required.

This is a pragmatic feasibility study to determine the impact of upfront brachytherapy combined with hypofractionated external beam radiation for patients with locally advanced cervical cancer (FIGO 2018 stage IB3-IVA) on late gastrointestinal and genitourinary toxicity, oncologic outcomes including recurrence free survival, and systemic and local immune response.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Cervical Carcinoma
• Intervention / Treatment: Drug: Chemotherapy; Radiation: Image-guided brachytherapy; Radiation: Hypofractionated external beam radiation

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jessika A Contreras, M.D.; Phone Number: 314-747-7236; Email: jcontreras@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Eric Laugeman, M.S.
      • Sub-Investigator: Premal H Thaker, M.D., M.S.
      • Sub-Investigator: Lindsay Kuroki, M.D., MSCI
      • Sub-Investigator: Esther Lu, Ph.D.
      • Sub-Investigator: Stephanie Markovina, M.D., Ph.D.
      • Sub-Investigator: Carolyn McCourt, M.D.
      • Sub-Investigator: Matthew A Powell, M.D.
      • Sub-Investigator: Dineo Khabele, M.D.
      • Sub-Investigator: Andrea Hagemann, M.D., MSCI
      • Sub-Investigator: Julie K Schwarz, M.D., Ph.D.
      • Contact: Jessika A Contreras, M.D.; Phone Number: 314-747-7236; Email: jcontreras@wustl.edu
      • Principal Investigator: Jessika A Contreras, M.D.
      • Sub-Investigator: David Lakomy, M.D.
      • Sub-Investigator: L. Stewart Massad, Jr., M.D.
      • Sub-Investigator: Brooke E Sanders, M.D.
      • Sub-Investigator: Shawn Wu, M.S.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Newly diagnosed biopsy proven FIGO (2018) clinical stage IB3-IVA cervical carcinoma.
• Histological diagnosis of squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix
• Candidate for definitive radiation therapy as determined by treating radiation oncologist.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representative may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• Any prior pelvic radiotherapy.
• Any prior gynecologic or other pelvic malignancy.
• Any prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for the trial.
• Evidence of metastatic disease outside of the pelvis or para-aortic nodes.
• Previous hysterectomy or planned hysterectomy as part of initial cervical cancer therapy; this includes patients with a prior history of supracervical hysterectomy.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test day of or within 7 days prior to simulation.
• Major surgery ≤ 3 weeks prior to initiating protocol therapy; if a patient has had major surgery prior to 3 weeks, they must have recovered from any surgical effects.
• Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled chronic obstructive pulmonary disease, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome.

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: Accelerated Brachytherapy Forward Chemo Radiation Therapy; Accelerated Brachytherapy Forward Chemo Radiation Therapy (ABC-RT) combines hypofractionated external beam radiation therapy (EBRT) with concurrent chemotherapy and early upfront, image-guided brachytherapy. In this study, patients start with 2 fractions of brachytherapy prior to initiation of EBRT-based chemoradiotherapy. Total time from treatment planning is approximately 36-42 days.

Drug: Chemotherapy; Concurrent chemotherapy are not dictated by the protocol and will follow standard of care guidelines; Radiation: Image-guided brachytherapy; HDR boost 7.3 Gy x 6 fractions; Radiation: Hypofractionated external beam radiation; Central pelvis (19.05 Gy in 15 fractions), nodal basins (40 Gy in 15 fractions), with a simultaneous integrated boost to grossly positive lymph nodes (48 Gy in 15 fractions)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late treatment related grade 3 or greater gastrointestinal and genitourinary adverse events experienced by participant	-Must be at least possibly related to RT.	Between day 91 and 2 year follow-up (estimated to be 2 years and 6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence-free survival (LRFS)	A local recurrence is defined as histologic or radiographic evidence of cancer in the cervix. Local recurrence-free survival is defined as the duration of time from the start of treatment to the time of local recurrence or death, whichever occurs first. The living patients with CR, PR, or SD in the cervix are censored at the corresponding date.	Up to 2 year follow-up (estimated to be 2 years and 6 weeks)
Regional recurrence-free survival (LRFS)	A regional recurrence is defined as histologic or radiographic evidence of cancer in the pelvic or para-aortic nodes. Regional recurrence-free survival is defined as the duration of time from the start of treatment to the time of regional recurrence or death, whichever occurs first. The living patients with CR, PR, or SD in the pelvis or para-aortic lymph nodes are censored at the corresponding date.	Up to 2 year follow-up (estimated to be 2 years and 6 weeks)
Progression-free survival (PFS)	Progression- free survival is defined as the duration of time from the start of treatment to progression or death, whichever occurs first. The living patients without progression are censored at the last follow-up.	Up to 2 year follow-up (estimated to be 2 years and 6 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jessika A Contreras, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2025
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: July 26, 2024
• First Posted (Actual): July 31, 2024

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 22, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pembrolizumab; Brachytherapy; Cervical cancer; Hypofractionated RT
• 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 Neoplasms; Uterine Cervical Neoplasms; Therapeutics; Drug Therapy
• Other Study ID Numbers: 202407064; R37CA287204 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Within 6 months of publication.
• IPD Sharing Access Criteria: Data will be available for investigators whose proposed use of the data has been approved by an independent review committee.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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