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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
- Geneesmiddel: Cisplatin
- Procedure: Biospecimen Collection
- Procedure: Magnetic Resonance Imaging
- Procedure: Computed Tomography
- Procedure: Positron Emission Tomography
- Straling: Intensity-Modulated Radiation Therapy
- Straling: Brachytherapy
- Straling: Radiation Boost
- Straling: Radiation Boost
- Straling: Hypofractionated External Beam Radiation Therapy
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 3
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Actieve vergelijker: 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
Andere namen:
Undergo blood sample collection
Andere namen:
Undergo MRI
Andere namen:
Undergo CT or PET/CT
Andere namen:
Undergo PET/CT
Andere namen:
Undergo IMRT
Andere namen:
Undergo brachytherapy
Andere namen:
Undergo integrated boost
Andere namen:
Undergo a nodal boost
Andere namen:
|
|
Experimenteel: 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
Andere namen:
Undergo blood sample collection
Andere namen:
Undergo MRI
Andere namen:
Undergo CT or PET/CT
Andere namen:
Undergo PET/CT
Andere namen:
Undergo brachytherapy
Andere namen:
Undergo integrated boost
Andere namen:
Undergo a nodal boost
Andere namen:
Undergo hypofractionated IMRT |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Progression-free survival (PFS)
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Rates of timely treatment completion
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Christina Henson, NRG Oncology
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Onderzoekstechnieken
- Therapeutica
- Klinische laboratoriumtechnieken
- Diagnostische technieken en procedures
- Diagnose
- Anorganische chemicaliën
- Chloorverbindingen
- Stikstofverbindingen
- Elementen
- Metalen
- Chemie -technieken, analytisch
- Spectrumanalyse
- Metalen, zwaar
- Platinumverbindingen
- Radiotherapie
- Overgangselementen
- Radiotherapie, conform
- Radiotherapie, computerondersteund
- Cisplatine
- 1,2-diaminocyclohexaanplatina II-citraat
- Exemplaarbehandeling
- Magnetische resonantiespectroscopie
- Platina
- Radiotherapie, intensiteit gemoduleerd
- Brachytherapie
Andere studie-ID-nummers
- NRG-GY039
- U10CA180868 (Subsidie/contract van de Amerikaanse NIH)
- NCI-2026-07269 (Register-ID: CTRP (Clinical Trial Reporting Program))
- NRG-GY039 (Andere identificatie: NRG Oncology)
- NRG-GY039 (Andere identificatie: CTEP)
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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