Daily Adaptive Radiation Therapy an Individualized Approach for Carcinoma of the Cervix (ARTIA-Cervix)

Daily Adaptive External Beam Radiation Therapy in the Treatment of Carcinoma of the Cervix: A Prospective Trial of an Individualized Approach for Intestinal Toxicity Reduction (ARTIA-Cervix)

This is a single-arm, prospective, multi-center clinical trial designed to demonstrate that adaptive radiotherapy for locally advanced cervical cancer will translate into a decreased rate of acute gastrointestinal toxicity compared with the historically reported rate for non-adaptive intensity modulated radiation therapy (IMRT). The timepoint for this assessment will be at week 5 of external beam radiotherapy (EBRT) and will use the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer by FIGO Stage 2018
• Intervention / Treatment: Device: Varian Ethos Adaptive Radiation Therapy

• Study Type: Interventional
• Enrollment (Estimated): 125
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sean Davidson, MS; Email: sean.davidson@varian.com
• Study Contact Backup: Name: Heike Hausen, MD; Phone Number: 1-650-743-7400; Email: heike.hausen@varian.com

Study Locations

• United States
  • Alabama
    • Burmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama Birmingham
      • Contact: Ashley Anderson; Phone Number: 205-975-2880; Email: aranderson@uabmc.edu
      • Contact: Cody Hughes; Email: codyhughes@uabmc.edu
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas Medical Sciences
      • Contact: Santanu Samanta, MD; Email: ssamanta@uams.edu
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • Moores Cancer Center at UC San Diego Health
      • Contact: Nicole Daniel; Email: mdaniel@health.ucsd.edu
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
      • Contact: Jeremy Price, MD; Email: jeremy.price@tuhs.temple.edu
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas Southwestern
      • Contact: Sarah Neufeld, MS; Phone Number: 214-648-1836; Email: Sarah.hardee@UTSouthwestern.edu
      • Contact: Kevin Albuquerque, MD; Email: kevin.albuquerque@utsouthwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients must have histologically confirmed, newly diagnosed advanced cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma): FIGO 2018 clinical stages IB2-IVA, without involved paraaortic lymph nodes.
2. For patients with involved pelvic lymph nodes, the upper border of the CTV nodal volume may not extend above the confluence of the common iliac arteries with the aorta (i.e., aortic bifurcation).
3. Patients must NOT have had a hysterectomy.
4. Pelvic nodal status is to be confirmed by one or more of the following studies/procedures: PET/CT scan, CT scan, MR Scan, fine needle biopsy, extra peritoneal biopsy or laparoscopic biopsy, per institutional standard of care.
5. Patients must be planning to undergo concurrent pelvic radiation and chemotherapy.
6. ECOG performance status ≤ 2 (Karnofsky ≥60%).
7. Patient must be willing and able to complete the PRO-CTCAE, EQ-5D, EPIC and EORTC questionnaires as described in the study protocol.

8. Patient must have normal organ and marrow function as defined below:

   • leukocytes ≥ 2,500/mcL
   • absolute neutrophil count ≥ 1,500/mcL
   • platelets ≥ 100,000/mcL
   • hemoglobin ≥ 8 g/dL (can be transfused with red blood cells pre-study)
   • total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
   • AST(SGOT)/ALT(SGPT) ≤ 3 × ULN
   • alkaline phosphatase ≤ 2.5 × ULN

   • creatinine < 1.5 mg/dL to receive weekly cisplatin*

     • Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for cisplatin if there is no hydronephrosis and the estimated creatinine clearance (CCr) is >30 ml/min. For the purpose of estimating the CCr, the formula of Cockcroft and Gault for females should be used:CCr=(0.85 ×(140-age)×IBW)/((Scr×72)) where age is the patient's age in years (from 20 to 80 years), Scr is the serum creatinine in mg/dL, and IBW is the ideal body weight in kg (according to the calculation IBW = 45.5 kg + 2.3 kg for each inch over 5 feet).
9. Age ≥ 18 years (or meets local age of consent).
10. Study participant is already intending to be prescribed a standard of care cisplatin treatment regimen.
11. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Prior radiation therapy to the pelvis or abdominal cavity, para-aortic lymph glands (PALN) radiation, or previous therapy of any kind for this malignancy.
2. Patients with PALN nodal metastasis.
3. Patients who have undergone staging pelvic and/or paraaortic lymphadenectomy.
4. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
5. Prior systemic anticancer therapy due to a diagnosis of cancer (e.g., chemotherapy, targeted therapy, immunotherapy) within 3 years prior to entering the study.
6. Patients diagnosed on imaging or biopsy with a synchronous primary malignancy (with the exception of DCIS of the breast, or early stage basal cell carcinoma of the skin).
7. Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease.
8. Patients with a history of other symptomatic autoimmune disease: rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's Granulomatosis); CNS or motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome and Myasthenia Gravis, multiple sclerosis.).
9. Patients with active tuberculosis (TB).
10. Patients who are pregnant.
11. Patients who are actively breastfeeding (or who do not agree to discontinue breastfeeding before the initiation of protocol therapy).
12. Patients who are of child-bearing potential who do not agree to use birth control (for a minimum of 14 months after the last dose of cisplatin) in accordance with institution's standard of care.
13. Patients with a prior known history or current diagnosis of a vesicovaginal, enterovaginal, or colovaginal fistula.
14. Patients who undergo a pelvic or para-aortic lymph node dissection prior to planned chemoradiation therapy.
15. Patients with known active infection of HIV.
16. Patients with hip prosthetics

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: Daily Adaptive External Beam Radiation Therapy; Daily adaptive radiation therapy delivered with Varian Ethos treatment system.	Device: Varian Ethos Adaptive Radiation Therapy; Daily adaptive external beam radiation therapy delivered on Varian Ethos treatment system.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Patient Reported Outcome (PRO) GI Toxicity	GI toxicity as reported by the patient using the gastrointestinal section of the NCI-PRO questionnaire	End of external beam treatment delivery (week 5)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute PRO Bowel Toxicity	Bowel toxicity as reported with EPIC bowel questionnaire	End of external beam treatment delivery (week 5)
Acute PRO Urinary Toxicity	Urinary toxicity as reported with EPIC urinary questionnaire	End of external beam treatment delivery (week 5)
Patient Reported Quality by EQ-5D-5L	Quality of life as document with EQ-5D-5L patient reported questionnaire	24 months post treatment
Patient Reported Quality by EORTC	Quality of life as document with EORTC patient reported questionnaire	24 months post treatment
Disease-free Survival	Disease-free survival at 2 years	Enrollment through 2 year follow up
Normal Tissue Complication Probability Model	Develop a normal tissue complication probability (NTCP) model of acute GI toxicity based on true integrated daily dose to the bowel	Enrollment through 2 year follow up
Workflow Feasibility	Record percentage of fractions delivered with adaptive radiation therapy vs traditional IGRT	End of external beam treatment delivery
CTCAE Toxicities	Physician reported CTCAE toxicities	Enrollment through 2 year follow up
Key powered secondary endpoint: Fecal Urgency	Acute reported fecal urgency (as measured by the inability to defer defecation by 15 minutes)	End of external beam treatment delivery (week 5)

Collaborators and Investigators

• Sponsor: Varian, a Siemens Healthineers Company
• Investigators: Principal Investigator: Jyoti Mayadev, MD, University of California, San Diego; Principal Investigator: Xenia Ray, PhD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: November 30, 2021
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Estimated): September 23, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: September 1, 2025

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; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Carcinoma; Uterine Cervical Neoplasms
• Other Study ID Numbers: VAR-2021-04

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: Yes
• product manufactured in and exported from the U.S.: No