Phase II Randomized Non-Inferiority Trial of Hypofractionated Radiotherapy for Locally Advanced Cervical Cancer in Uganda
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 278
- 试验地点
- 1
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
This phase II trial compares the effect of hypofractionated radiotherapy (HFRT) to conventional fractionated radiotherapy (CFRT) when given in combination with cisplatin and brachytherapy in patients with stage IB3, II, or III cervical cancer. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. CFRT delivers the total dose of radiation over the amount of time according to standard practice. HFRT delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. HFRT shortens treatment duration and may reduce costs and may improve the completion rates. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. HFRT may be safe, tolerable, and/or as effective as CFRT when given in combination with cisplatin and brachytherapy in treating patients with stage IB3, II or III cervical cancer.
详细描述
PRIMARY OBJECTIVE:
I. To determine the safety, and efficacy of hypofractionated radiotherapy (40 Gy in 16 fractions) compared to conventional fractionated radiotherapy (45 Gy in 25 fractions) in women with locally advanced cervical cancer in Uganda.
SPECIFIC OBJECTIVES:
I. To compare the incidence of grade 3+ gastrointestinal and genitourinary toxicity at 1- and 2-years post-treatment with hypofractionated radiotherapy (40 Gy in 16 fractions) and conventional fractionated radiotherapy (45 Gy in 25 fractions) in women with cervical cancer in Uganda.
II. To evaluate and compare local control and cervical cancer-specific survival rates at 1 and 2 year after hypofractionated radiotherapy (40 Gy in 16 fractions) versus conventional radiotherapy (45 Gy in 25 fractions).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This study does not provide for blinding of participants or providers due to the significant differences between the study intervention and control in terms of the duration of treatment, three weeks compared to five weeks of external beam radiotherapy. However, information bias will be minimized by ensuring that data collectors (research staff) are not directly involved in the delivery of treatment for study patients
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females aged 18 years or older
- •Histologically confirmed squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the uterine cervix without prior treatment
- •Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3, IIA, IIB, IIIA, IIIB, or IIIC
- •Able to provide written informed consent in English, Luganda, Runyankole, or Lango
- •Willing to attend post-treatment follow-up for up to 12 months
- •Fit for concurrent chemotherapy with cisplatin
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2
- •Absolute neutrophil count ≥ 1,500 cells/mm^3 (1.5 x 10^9/L)
- •Platelets ≥ 100,000 cells/mm^3 (100 x 10^9/L)
- •Hemoglobin ≥ 9.0 g/dL
- •Leukocyte count ≥ 4,000 cells/mm^3 (4.0 x 10^9/L)
- •Creatinine clearance > 60 mL/mins, calculated using the Cockcroft-gault equation for women
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the upper limit of normal (ULN)
- •Total bilirubin < 2 x ULN unless attributed to the use of antiretroviral therapy (ART)
- •HIV-positive participants must be on a stable ART regimen for at least 6 weeks prior to enrollment
排除标准
- •Prior hysterectomy. Women with previous total or subtotal hysterectomy have no cervix, and hence the anatomical changes have an impact on the radiotherapy field, and dose prescriptions because they tend to have a higher risk for bowel toxicity from pelvic radiotherapy. Therefore, these women will be excluded due to the likely impact on the results of our study intervention
- •Clinical and/or radiological evidence of distant metastases
- •Prior pelvic or abdominal radiotherapy
- •Presence of bilateral hip prosthesis that could interfere with radiotherapy treatment
- •History of inflammatory bowel disease or any other condition that could complicate radiotherapy treatment
- •Participants who are pregnant at the time of enrollment. Pregnant women have a potential risk of radiation exposure to developing fetus, which may result in fetal malformations, growth retardation, or even fatal death. Secondly, their physiological changes alter the pharmacokinetics and pharmacodynamics of concurrent chemotherapy. Therefore, to protect the health of the mother and the unborn child, pregnant women will be excluded from the study. Patients who are found to be pregnant after enrollment will have the study procedures terminated
- •Concurrent untreated invasive malignancy
- •Uncontrolled concurrent medical/psychiatric diagnosis that would limit compliance with study requirements
- •Uncontrolled HIV infection, especially HIV viral load > 2,000 copies/mL
- •Participants with CD4 counts < 200 cells/mm^3
研究组 & 干预措施
Arm I (HFRT)
Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Hypofractionated Radiation Therapy (Radiation)
Arm I (HFRT)
Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Cisplatin (Drug)
Arm I (HFRT)
Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: High-Dose Rate Brachytherapy (Radiation)
Arm I (HFRT)
Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: External Beam Radiotherapy Boost (Radiation)
Arm I (HFRT)
Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm I (HFRT)
Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (HFRT)
Patients undergo HFRT QD, Monday-Friday, for 5 fractions weekly for 16 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Questionnaire and Physical Exam (Other)
Arm II (CFRT)
Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Conventional Fractionated Radiotherapy (Radiation)
Arm II (CFRT)
Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Cisplatin (Drug)
Arm II (CFRT)
Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: High-Dose Rate Brachytherapy (Radiation)
Arm II (CFRT)
Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: External Beam Radiotherapy Boost (Radiation)
Arm II (CFRT)
Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Computed Tomography (Procedure)
Arm II (CFRT)
Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (CFRT)
Patients undergo CFRT QD, Monday-Friday, for 5 fractions weekly for up to 25 fractions in the absence of disease progression or unacceptable toxicity. Starting on day 1 of radiation therapy, patients receive cisplatin infusion over 1 hour QW during radiation therapy. Starting by week 4, patients may also undergo HDR brachytherapy twice weekly for a total of 4 doses. Patients ineligible for brachytherapy undergo a sequential external beam boost. Additionally, patients undergo CT and blood sample collection throughout the study.
干预措施: Questionnaire and Physical Exam (Other)
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: Up to 90 days post-treatment
It will be categorized into 5 grades. The Conchran-Mantel-Haenszel test will be used to compare differences in the grades of AEs between patients who will receive hypofractionated radiotherapy versus conventional fractionated radiotherapy by stratifying for HIV status. A p-value of \< 5% will be regarded as significant.
Incidence of grade 3 or greater radiotherapy-related gastrointestinal or genitourinary AEs
时间窗: At 1 and 2 years post-treatment
Will compare the proportion of patients between the hypofractionated radiotherapy and conventional fractionated radiotherapy using a risk difference approach, and the 95% confidence interval (CI) for the difference in proportion will be estimated using the Farrington-Manning test. Non-inferiority will be determined when the upper bound of a two-sided 95% CI is less than 10%.
Local control (complete remission, stable disease, and partial response) rate
时间窗: At 1 and 2 years post-treatment
Will be compared using means, medians, standard deviations, and ranges for continuous variables and frequencies and percentages for categorical variables. Differences in local control for each treatment group and the 95% CI will be calculated using the Chi-square test or Fisher's exact test. Data on tumor sizes that are normally distributed will be presented as means and standard deviations with 95% CI. The log-rank test will be used to compare the local control rates. The mean difference between groups will be calculated using an independent T-test for normally distributed data. Will compare the proportion between arms using a risk difference approach and the 95% CI, the difference in proportion will be estimated using the Farrington-Manning test. Non-inferiority will be determined when the upper bound of a two-sided 95% Confidence interval is less than 10%.
次要结局
- Cervical cancer-specific survival(At 1 and 2 years post-treatment)
- Progression-free survival (PFS)(From randomization to the date of first recurrence or progression of disease or death, assessed up to 2 years)