Daily Adaptive Radiation Therapy an Individualized Approach for Carcinoma of the Cervix

Study Overview
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Brief Summary
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This is a single-arm, prospective, Phase II, 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).

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

Conditions
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Cervical Cancer by FIGO Stage 2018

Intervention / Treatment
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* Device: Varian Ethos Adaptive Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 positive LN. Patients must NOT have had a hysterectomy. 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. Patients must be planning to undergo concurrent pelvic radiation and chemotherapy. ECOG performance status ≤ 2 (Karnofsky ≥60%). Patient must be willing and able to complete the PRO-CTCAE, EQ-5D, EPIC and EORTC questionnaires as described in the study protocol. 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). Age ≥ 18 years. No known allergy to cisplatin or compounds of similar biologic composition. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Prior radiation therapy to the pelvis or abdominal cavity, para-aortic lymph glands (PALN) radiation, or previous therapy of any kind for this malignancy. Patients with PALN nodal metastasis. Prior allogeneic bone marrow transplantation or prior solid organ transplantation. Prior systemic anticancer therapy due to a diagnosis of cancer (e.g., chemotherapy, targeted therapy, immunotherapy) within 3 years prior to entering the study. 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). Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease. 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.). Patients with active tuberculosis (TB). Patients who are pregnant. Patients who are actively breastfeeding (or who do not agree to discontinue breastfeeding before the initiation of protocol therapy). Patients who are of child-bearing potential who do not agree to use birth control in accordance with institution's standard of care. Patients with a prior known history or current diagnosis of a vesicovaginal, enterovaginal, or colovaginal fistula. Patients who undergo a pelvic or para-aortic lymph node dissection prior to planned chemoradiation therapy. Patients with active infection of HIV; positive 1 / 2 antibodies. Patients with hip prosthetics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily Adaptive External Beam Radiation Therapy<br>Daily adaptive radiation therapy delivered with Varian Ethos treatment system. | Device: Varian Ethos Adaptive Radiation Therapy<br>* Daily adaptive external beam radiation therapy delivered on Varian Ethos treatment system.<br>|

What is the study measuring?
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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 |