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

• ClinicalTrials.gov Identifier: NCT05197881
• Recruitment Status: Recruiting
• First Posted: January 20, 2022
• Last Update Posted: May 10, 2024
• Sponsor: Varian, a Siemens Healthineers Company
• Information provided by (Responsible Party): Varian, a Siemens Healthineers Company

Tracking Information

• First Submitted Date: November 30, 2021
• First Posted Date: January 20, 2022
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: May 3, 2022
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 13, 2022)

Acute Patient Reported Outcome (PRO) GI Toxicity [ Time Frame: End of external beam treatment delivery (week 5) ]

GI toxicity as reported by the patient using the gastrointestinal section of the NCI-PRO questionnaire

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 7, 2024)

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

Original Secondary Outcome Measures (submitted: January 13, 2022)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Daily Adaptive Radiation Therapy an Individualized Approach for Carcinoma of the Cervix
• Official Title: 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)
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cervical Cancer by FIGO Stage 2018

Intervention

Device: Varian Ethos Adaptive Radiation Therapy

Daily adaptive external beam radiation therapy delivered on Varian Ethos treatment system.

Study Arms

Experimental: Daily Adaptive External Beam Radiation Therapy

Daily adaptive radiation therapy delivered with Varian Ethos treatment system.

Intervention: Device: Varian Ethos Adaptive Radiation Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 13, 2022): 125
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2028
• Estimated Primary Completion Date: May 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Steve Kohlmyer, MS; 12062760076; steve.kohlmyer@varian.com

Contact: Sean Davidson, MS; sean.davidson@varian.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05197881
• Other Study ID Numbers: VAR-2021-04
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Varian, a Siemens Healthineers Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Varian, a Siemens Healthineers Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jyoti Mayadev, MD; University of California, San Diego
• Principal Investigator: Xenia Ray, PhD; University of California, San Diego

• PRS Account: Varian, a Siemens Healthineers Company
• Verification Date: May 2024