Study to Test Shorter Duration Chemoradiation Therapy Versus Standard Duration Chemoradiation Therapy for Cervical Cancer
A Phase III Non-Inferiority Trial of Hypofractionated Chemoradiation Therapy Versus Standard Chemoradiation for Cervical Cancer
This phase III trial compares the effect of a shorter duration (hypofractionated) of intensity-modulated radiation therapy (IMRT) with brachytherapy and cisplatin to standard duration IMRT with brachytherapy and cisplatin in treating patients with newly diagnosed stage IB2-IIIC1 cervical cancer. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. IMRT is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. A radiation boost is extra radiation to the area where the tumor is located which increases the amount of radiation given to the tumor bed. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving hypofractionated chemoradiation therapy may be as safe, tolerable and/or effective as the standard, longer course of chemoradiation therapy in treating patients newly diagnosed with stage IB2-IIIC1 cervical cancer.
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
- Drog: Cisplatin
- Eljárás: Biospecimen Collection
- Eljárás: Magnetic Resonance Imaging
- Eljárás: Computed Tomography
- Eljárás: Positron Emission Tomography
- Sugárzás: Intensity-Modulated Radiation Therapy
- Sugárzás: Brachytherapy
- Sugárzás: Radiation Boost
- Sugárzás: Radiation Boost
- Sugárzás: Hypofractionated External Beam Radiation Therapy
Részletes leírás
PRIMARY OBJECTIVE:
I. To determine if hypofractionated IMRT with concurrent cisplatin and brachytherapy boost is non-inferior to conventionally fractionated treatment with respect to progression-free survival (PFS).
SECONDARY OBJECTIVES:
I. To estimate the rates of timely treatment completion. II. To determine the nature and degree of toxicity of hypofractionated IMRT with concurrent cisplatin and brachytherapy as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.
III. To evaluate late toxicity, progression-free survival, and overall survival (OS) at 3 years.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients undergo IMRT with a simultaneous integrated boost once daily (QD) on Monday-Friday weekly for up to 5 weeks (25 treatment fractions) followed by brachytherapy for up to 3-5 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients receive cisplatin intravenously (IV) once weekly (QW) for up to 5 cycles while undergoing IMRT in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and positron emission tomography (PET)/computed tomography (CT), CT, or magnetic resonance imaging (MRI) throughout the study.
ARM 2: Patients undergo hypofractionated IMRT QD on 5 days per week for up to 3-4 weeks (15 treatment fractions) then a nodal boost (if indicated) for up to 4 treatment fractions followed by brachytherapy for up to 3-5 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients receive cisplatin IV QW for up to 5 cycles while undergoing IMRT in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET/CT, CT, or MRI throughout the study.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years then every 6 months for up to 3 years.
Tanulmány típusa
Beiratkozás (Becsült)
Fázis
- 3. fázis
Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
Inclusion Criteria:
- Patients must have histologically confirmed newly diagnosed cervical cancer. Eligible pathologic types: squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma
- Patients must have a diagnosis of Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 (T1B2, N0), stage IB3 (T1B3N0), II (T2A-B, N0), IIIC1 (T1B2-3, N1), or IIIC1 (T2A-B, N1) squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix not amenable to curative surgical resection alone
- Negative for para-aortic disease AND treating physician does not plan to treat para-aortic nodes
- Radiologic definition of lymph node staging:
N1:
-
One or more pelvic lymph nodes with short axis diameter of ≥ 15 mm (axial plane) by CT or MRI, and/or
-
One or more pelvic lymph nodes with short axis diameter of ≥ 10 mm and standarized uptake value maximum (SUVmax) ≥ 2.5 by fludeoxyglucose F-18 (FDG)-PET
- No prior definitive surgical, radiation, or systemic therapy for cervical cancer. Induction chemotherapy with weekly carboplatin (area under curve [AUC]2) and paclitaxel (80 mg/m^2) for up to 6 weeks is allowed prior to study entry. This is the only permissible induction chemotherapy regimen prior to study entry
- No prior or concurrent immunotherapy
- No prior pelvic radiation therapy
- Age ≥/= 18
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Not pregnant and not nursing
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
- Platelets ≥ 100,000 cells/mm^3
- Hemoglobin ≥ 8 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin [Hgb] ≥ 8 g/dl is acceptable)
- Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II B or better
- No active infection requiring parenteral antibiotics
- No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
- No history of allergic reaction to cisplatin or compounds of similar chemical or biologic composition
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
|
Aktív összehasonlító: Arm 1 (standard IMRT, brachytherapy, cisplatin)
Patients undergo IMRT with a simultaneous integrated boost QD on Monday-Friday weekly for up to 5 weeks (25 treatment fractions) followed by brachytherapy for up to 3-5 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients receive cisplatin IV QW for up to 5 cycles while undergoing IMRT in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET/CT, CT, or MRI throughout the study. |
Given IV
Más nevek:
Undergo blood sample collection
Más nevek:
Undergo MRI
Más nevek:
Undergo CT or PET/CT
Más nevek:
Undergo PET/CT
Más nevek:
Undergo IMRT
Más nevek:
Undergo brachytherapy
Más nevek:
Undergo integrated boost
Más nevek:
Undergo a nodal boost
Más nevek:
|
|
Kísérleti: Arm 2 (hypofractionated IMRT, brachytherapy, cisplatin)
Patients undergo hypofractionated IMRT QD on 5 days per week for up to 3-4 weeks (15 treatment fractions) then a nodal boost (if indicated) for up to 4 treatment fractions followed by brachytherapy for up to 3-5 treatment fractions in the absence of disease progression or unacceptable toxicity. Patients receive cisplatin IV QW for up to 5 cycles while undergoing IMRT in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection and PET/CT, CT, or MRI throughout the study. |
Given IV
Más nevek:
Undergo blood sample collection
Más nevek:
Undergo MRI
Más nevek:
Undergo CT or PET/CT
Más nevek:
Undergo PET/CT
Más nevek:
Undergo brachytherapy
Más nevek:
Undergo integrated boost
Más nevek:
Undergo a nodal boost
Más nevek:
Undergo hypofractionated IMRT |
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Progression-free survival (PFS)
Időkeret: From randomization to first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 3 years
|
Tests will be based on stratified log-rank tests to assess the randomized treatment effect among all randomized patients. Analyses will be supported by the intent-to-treat population, with patients analyzed according to their randomized treatment assignment. The log-rank tests will be stratified by the factor recorded at randomization. The treatment hazard ratio estimates and their 95% confidence intervals for the interim and primary analyses will be estimated using Cox proportional hazards models specified with a main effect for the randomized treatment assignment and stratified by the factor recorded at randomization. |
From randomization to first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 3 years
|
Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Rates of timely treatment completion
Időkeret: From initiation of the assigned protocol therapy to treatment completion, assessed up to 46 days (for control arm) and up to 56 days (for experimental arm)
|
Will be defined as completing treatment within the protocol specified timeframes. Will be estimated for each treatment arm using binomial method, with corresponding confidence intervals, and the difference between treatment arms will be evaluated using 2-sided Fisher's exact test. |
From initiation of the assigned protocol therapy to treatment completion, assessed up to 46 days (for control arm) and up to 56 days (for experimental arm)
|
|
Incidence of acute adverse events (AEs)
Időkeret: Up to 30 days after last dose of study treatment
|
The nature, frequency, and degree will be tabulated at the system organ class and AE-specific term levels using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0. Each patient will be represented by the maximum grade observed for each term. Tabulations will present the number and percentage of patients by maximum grade, within the treatment group received, regardless of the randomized treatment assignment. Will be dichotomized as severe (grade 3 or higher) or non-severe (grade 2 or lower). The proportion of patients experiencing severe toxicity will be estimated for each arm using the binomial method. The difference in proportions (experimental minus control) and its two-sided 90% confidence interval will be calculated. A 2-sided Fisher's exact test will be used to evaluate whether the distribution of severe toxicity differs between the 2 arms at 10% significance level. |
Up to 30 days after last dose of study treatment
|
|
Incidence of late AEs
Időkeret: During follow-up beyond 30 days after stopping protocol treatment, assessed up to 3 years
|
The nature, frequency, and degree will be tabulated at the system organ class and AE-specific term levels using CTCAE v 5.0. Each patient will be represented by the maximum grade observed for each term. Tabulations will present the number and percentage of patients by maximum grade, within the treatment group received, regardless of the randomized treatment assignment. Will be dichotomized as severe (grade 3 or higher) or non-severe (grade 2 or lower). The proportion of patients experiencing severe toxicity will be estimated for each arm using the binomial method. The difference in proportions (experimental minus control) and its two-sided 90% confidence interval will be calculated. A 2-sided Fisher's exact test will be used to evaluate whether the distribution of severe toxicity differs between the 2 arms at 10% significance level. |
During follow-up beyond 30 days after stopping protocol treatment, assessed up to 3 years
|
|
PFS
Időkeret: At 3 years
|
Will be estimated for each arm using Kaplan-Meier method. The distributions by treatment arm will be illustrated with Kaplan-Meier curves. |
At 3 years
|
|
Overall survival
Időkeret: At 3 years
|
Will be estimated for each arm using Kaplan-Meier method. The distributions by treatment arm will be illustrated with Kaplan-Meier curves. The treatment effect (Arm 2 versus Arm 1) will be evaluated using a 2-sided log-rank test, stratified by the factor specified at randomization. The hazard ratio and its 95% confidence intervals will be estimated using a Cox proportional hazards model, including main effects for the randomized treatment assignment (Arm 2 vs Arm 1) and stratified by the factor specified at randomization. |
At 3 years
|
Együttműködők és nyomozók
Szponzor
Együttműködők
Nyomozók
- Kutatásvezető: Christina Henson, NRG Oncology
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Becsült)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
- Nyomozási technikák
- Terápiás kezelés
- Klinikai laboratóriumi technikák
- Diagnosztikai technikák és eljárások
- Diagnózis
- Szervetlen vegyi anyagok
- Klórvegyületek
- Nitrogénvegyületek
- Elemek
- Fémek
- Kémiai technikák, analitikus
- Spektrumelemzés
- Fémek, nehéz
- Platinavegyületek
- Sugárterápia
- Átmeneti elemek
- Sugárterápia, konformális
- Sugárterápia, számítógépes segített
- Ciszplatin
- 1,2-diamino-ciklohexán-platina-II citrát
- Minta kezelése
- Mágneses rezonancia spektroszkópia
- Platina
- Sugárterápia, intenzitás-modulált
- Brachiterápia
Egyéb vizsgálati azonosító számok
- NRG-GY039
- U10CA180868 (Az Egyesült Államok NIH támogatása/szerződése)
- NCI-2026-07269 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- NRG-GY039 (Egyéb azonosító: NRG Oncology)
- NRG-GY039 (Egyéb azonosító: CTEP)
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