Adaptive radiation therapy for cervical cancer

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 study is testing if a new type of radiation therapy can help reduce stomach and bowel problems in people with advanced cervical cancer who are also getting chemotherapy.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 125 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Varian, a Siemens Healthineers Company (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 5 sites (Burmingham, Alabama and 4 other locations)
• Trial ID: NCT05197881 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of adaptive radiotherapy in reducing acute gastrointestinal toxicity in patients with locally advanced cervical cancer. It is a single-arm, prospective, multi-center trial that will assess patient-reported outcomes at week 5 of external beam radiotherapy. The study will involve patients receiving Varian Ethos Adaptive Radiation Therapy while undergoing concurrent pelvic radiation and chemotherapy. The results will be compared to historical data from non-adaptive intensity modulated radiation therapy.

Who should consider this trial

Good fit: Ideal candidates include patients with newly diagnosed advanced cervical cancer (FIGO stages IB2-IVA) who are planning to receive concurrent pelvic radiation and chemotherapy.

Not a fit: Patients who have had a hysterectomy or have involved paraaortic lymph nodes may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to reduced gastrointestinal side effects for patients undergoing treatment for cervical cancer.

How similar studies have performed: While adaptive radiation therapy is a growing field, this specific approach for cervical cancer is relatively novel and has not been extensively tested in prior studies.

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

Where this trial is running

Burmingham, Alabama and 4 other locations

• University of Alabama Birmingham — Burmingham, Alabama, United States (Recruiting)
• University of Arkansas Medical Sciences — Little Rock, Arkansas, United States (Recruiting)
• Moores Cancer Center at UC San Diego Health — La Jolla, California, United States (Recruiting)
• Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States (Recruiting)
• University of Texas Southwestern — Dallas, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Jyoti Mayadev, MD — University of California, San Diego
• Study coordinator: Heike Hausen, MD

Conditions Cervical Cancer by FIGO Stage 2018