Pelvic RT Versus Prophylactic Extended-field RT in Patients With Cervical Cancer

Uterine Cervical Neoplasms Clinical Trial

Official title:

Pelvic Irradiation Versus Prophylactic Extended-field Irradiation in Selected Patients With Cervical Cancer Treated With Concurrent Chemoradiotherapy: A Multicenter, Open-label, Randomized, Phase 3 Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03955367
• Other study ID #: PUMCH-EFI
• Status: Recruiting
• Phase: Phase 3
• Start date: June 17, 2019
• Est. completion date: June 1, 2025

Study information

• Verified date: February 2022
• Source: Peking Union Medical College Hospital
• Contact: Ke Hu
• Phone: +86-01069155487
• Email: huk[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To investigate the value of prophylactic extended-field irradiation (EFI), we conduct a randomized clinical trial to compare the efficacy and toxicity of pelvic irradiation and prophylactic EFI in selected patients with cervical cancer treated with definitive concurrent chemoradiotherapy. External beam radiation therapy is delivered with intensity-modulated radiation therapy (IMRT).

Description:

This is a multicenter, open-label, phase III randomized clinical trial. Cervical cancer patients without evidence of para-aortic metastatic lymph nodes (MLNs) and with at least one of the following characteristics are included in the present study: (a) Number of pelvic MLNs ≥ 2; (b)Short diameter of pelvic MLNs ≥ 1.5cm; (c)Pelvic wall involvement. Patients are randomly assigned to pelvic irradiation group and prophylactic EFI group. Patients in pelvic irradiation group receive pelvic irradiation, intracavitary brachytherapy and concurrent chemotherapy. Patients in prophylactic EFI group receive irradiation for pelvis and para-aortic lymph nodes region, intracavitary brachytherapy and concurrent chemotherapy. The upper border of clinical target volume (CTV) is at the level of renal vessels for patients in prophylactic EFI group. A dose of 45-50.4 Gy is delivered to CTV with IMRT in both groups. Patients receive cisplatin based concurrent chemotherapy (single cisplatin or cisplatin plus paclitaxel). The primary endpoint is progression-free survival.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 638
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Patients must be informed of the investigational nature of this study and give written informed consent with 30 days before treatment.

2. Age =18 years and = 70 years.

3. Patients with newly histologically confirmed cervical cancer, including squamous cell carcinoma, adenocarcinoma and adenosquamous carcinoma, et al.

4. No evidence of para-aortic metastatic lymph nodes (MLNs) on CT, MRI or positron emission tomograph (PET)/CT.*

5. No evidence of distant metastasis (FIGO stage IVB).

6. At least meet one of the following characteristics:

1. Number of pelvic MLNs = 2;

2. Short diameter of pelvic MLNs = 1.5cm; *

3. Parametrial involvement to the pelvic wall #.

7. Satisfactory performance: Eastern Cooperative Oncology Group (ECOG) score = 2.

8. Adequate marrow: neutrophile granulocyte count =1.5*10^9/L, hemoglobin = 80 g/L, platelet count =100*10^9/L.

9. Normal liver and kidney function: Creatinine (Cr) < 1.5 mg/dl, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) < 2*upper limit of normal (ULN).

• MLNs refer to positive lymph nodes confirmed by PET/CT or lymph nodes with short diameter = 1 cm on CT or MRI.

• Parametrial involvement to the pelvic wall is diagnosed with gynecological examination or MRI;

Exclusion Criteria:

1. With common iliac MLNs.

2. Tumor extended to the lower third of the vagina.

3. Tumor spread to mucosa of the bladder or rectum.

4. Prior surgery (including pelvic or para-aortic lymph nodes resection, except for tumor biopsy), radiotherapy or chemotherapy to primary tumor or nodes.

5. Prior malignancy.

6. History of previous radiotherapy to the abdomen or pelvis.

7. Pregnancy or lactation.

8. Active inflammatory bowel disease, or history of severe stomach or duodenal ulcer.

9. Active infection with fever.

10. Patients with unacceptable risk that intracavitary brachytherapy can not be conducted.

11. Any severe disease which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control, and emotional disturbance.

Related Conditions & MeSH terms

• Uterine Cervical Neoplasms

Intervention

Radiation:
• Prophylactic extended-field Irradiation
CTV covers pelvis and para-aortic lymph nodes region.
• Pelvic irradiation
CTV covers pelvis.
• Intracavitary brachytherapy
The total dose delivered to point A or high-risk CTV is =80Gy. For patients with larger-volume cervical tumor, the total dose is =85Gy.

Drug:
• Concurrent chemotherapy
Cisplatin based concurrent chemotherapy, including cisplatin as a single agent or cisplatin plus Paclitaxel.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing	Beijing
China	First Affiliated Hospital Xi'an Jiaotong University	Xi'an	Shanxi

Sponsors (35)

Lead Sponsor

Collaborator

Peking Union Medical College Hospital

Affiliated Cancer Hospital of Zhengzhou University, Beijing Obstetrics and Gynecology Hospital, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Cangzhou Central Hospital, China-Japan Union Hospital, Jilin University, First Affiliated Hospital of Chongqing Medical University, First Affiliated Hospital of Guangxi Medical University, First Affiliated Hospital Xi'an Jiaotong University, General Hospital of Benxi Iron & Steel Industry Group, General Hospital of Ningxia Medical University, Guizhou Provincial People's Hospital, Harbin Medical University Third Affiliated Hospital, Henan Provincial People's Hospital, Jiangsu Cancer Institute & Hospital, Jilin Provincial Tumor Hospital, Peking University First Hospital, Second Affiliated Hospital of Xi'an Jiaotong University, Second Hospital of Jilin University, Seventh Medical Center of PLA Army General Hospital, Shengjing Hospital, Tangshan People's Hospital, The 940th Hospital of Joint Logistics Support Force,PLA., The Affiliated Hospital of Inner Mongolia Medical University, The Affiliated Tumor Hospital of Xinjiang Medical University, The First Affiliated Hospital of Zhengzhou University, The Forth Affiliated Hospital of Guangxi Medical University, The Second Affiliated Hospital of Dalian Medical University, Tumor Hospital of Gansu, West China Second University Hospital, Wuhan Union Hospital, China, Xi'an Gaoxin Hospital, Xiangya Hospital of Central South University, Zhejiang Cancer Hospital, Zhongnan Hospital of Wuhan University & Second Clinical Hospital of Wuhan University

Country where clinical trial is conducted

China, 

References & Publications (1)

Wang W, Liu X, Meng Q, Zhang F, Hu K. Prophylactic Extended-Field Irradiation for Patients With Cervical Cancer Treated With Concurrent Chemoradiotherapy: A Propensity-Score Matching Analysis. Int J Gynecol Cancer. 2018 Oct;28(8):1584-1591. doi: 10.1097/IGC.0000000000001344. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever is first.	3-year
Secondary	Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year
Secondary	Distant failure-free survival	Distant failure-free survival is defined as the time from randomization to distant metastasis or death from any cause, whichever is first.	3-year
Secondary	Para-aortic lymph nodes failure rate	The incidence of para-aortic lymph nodes failure.	3-year
Secondary	Acute toxicity evaluated with CTCAE 5.0	Evaluated with CTCAE 5.0	From the start of treatment to 3 months after treatment.
Secondary	Late toxicity evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme	Evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme	3-year