GCCC 2578 Randomized Photon vs Proton RT for Newly Diagnosed Gynecologic Primaries

A Phase II, Randomized, Open-Label, Single-Center Study Comparing Intensity Modulated Proton Therapy Versus Volume Modulated Arc Therapy in Patients Receiving Pelvic Nodal Irradiation for Newly Diagnosed Gynecologic Primaries

The purpose of study is to compare the side effects of two different forms of radiation for endometrial and cervical cancer. If you decide to enroll in this study, you will be randomized to one of two treatment groups. This study will compare two standard of care treatments: "Conventional" pHoton radiation versus pRoton radiation.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer; Radiation Therapy; Gynaecologic Cancer
• Intervention / Treatment: Radiation: Volume Modulated Arc Therapy (VMAT); Radiation: Intensity Modulated Proton Therapy (IMPT)

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Elizabeth Nichols, MD; Phone Number: 410-328-6080; Email: enichols1@umm.edu
• Study Contact Backup: Name: Caitlin Eggleston, MPH; Phone Number: 410-369-5351; Email: caitlineggleston@umm.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
    • Baltimore, Maryland, United States, 21201
      • Maryland Proton Treatment Center
    • Bel Air, Maryland, United States, 21014
      • Upper Chesapeake Health
    • Columbia, Maryland, United States, 21044
      • Central Maryland Radiation Oncology
    • Glen Burnie, Maryland, United States, 21061
      • Baltimore Washington Medical Center- Tate Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. a. Newly diagnosed endometrial cancer after TAH/BSO and nodal sampling, sentinel LN biopsy or pelvic nodal dissection planning to receive sequential chemotherapy and radiation or concurrent chemoradiotherapy or b. cervical cancer planning to receive definitive chemoradiation with HDR brachytherapy boost
2. Histologic confirmation of malignancy (primary only)
3. ≥ 18 years of age
4. ECOG performance status ≤ 2
5. Patient must have the ability to understand and the willingness to sign a written informed consent document or when appropriate, have an acceptable surrogate capable of giving consent on the subject's behalf.
6. Insurance approval for IMPT

Exclusion Criteria:

1. Metastatic disease beyond para-aortic lymph nodal region
2. Residual tumor after surgery exceeding 2 cm in maximum dimension in patients with endometrial cancer.
3. FIGO 2014 stage III-IVA cervix cancer planning to receive concurrent pembrolizumab.
4. Cervical cancer with inability to receive concurrent chemotherapy.
5. Any prior pelvic radiation.
6. Treatment with other investigational agents.
7. Carcinosarcoma.
8. Creatine clearance <30 mL/m2
9. Unable to lie flat during or tolerate radiation.
10. Refusal to sign informed consent.
11. Any additional active cancer that would interfere with the primary study endpoints

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Photon Radiation; Photon Radiation Therapy (Volume Modulated Arc Therapy (VMAT))	Radiation: Volume Modulated Arc Therapy (VMAT); VMAT RT- 45-50.4 Gy in 1.8-2 Gy fractions All patients will receive concurrent cisplatin 40 mg/m2 on a weekly basis during EBRT in accordance with standard of care. No chemotherapy will be utilized during HDR brachytherapy.; Other Names: Arm 1
Active Comparator: Proton Radiation; Proton Radiation Therapy (Intensity Modulated Proton Therapy (IMPT))	Radiation: Intensity Modulated Proton Therapy (IMPT); IMPT- 45-50.4 Gy in 1.8-2 Gy fractions All patients will receive concurrent cisplatin 40 mg/m2 on a weekly basis during EBRT in accordance with standard of care. No chemotherapy will be utilized during HDR brachytherapy.; Other Names: Arm 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related Acute Gastrointestinal Toxicity as assessed by CTCAE v 5.0	To compare patient reported acute gastrointestinal toxicity specifically grade 2 or higher (CTCAE) diarrhea events between IMPT and VMAT for patients receiving pelvic nodal irradiation for newly diagnosed cervical and endometrial cancer.	2-years following completion of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of grade 4 (via CTCAE) lymphopenia during radiation between IMPT and VMAT	To compare the incidence of grade 4 lymphopenia during radiation between IMPT and VMAT for patients receiving pelvic nodal irradiation for newly diagnosed cervical and endometrial cancer.	2-year following completion of treatment
Number of patients with decreased lymphocyte values at first follow-up visit post radiation	To compare lymphocyte nadir at first follow-up visit after completion of radiation.	3 months post completion of RT
Number of patients with physician reported GI toxicities assessed by CTCAE v5	To compare physician reported GI outcomes between arms.	2 years post radiation treatment
Rates of treatment completion within scheduled time frame	To compare rates of treatment completion within scheduled time frame between arms.	2 years post treament
GI, GU and hematologic grade 2 or higher late toxicity events (via CTCAE)	To compare GI, GU and hematologic grade 2 or higher late toxicity events between arms.	2 years post treatment completion
Compare 2-year overall survival, local failure and distant failure	To compare 2-year overall survival, local failure and distant failure between arms.	2 years post treatment completion

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Elizabeth Nichols, MD, University of Maryland Medical Center/Maryland Proton Treatment Center

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2033

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• 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; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy, Intensity-Modulated; DMAC2L protein, human
• Other Study ID Numbers: HP-00116109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No