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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Uterine Cervical Neoplasms
• Intervention / Treatment: Radiation: Pelvic irradiation; Radiation: Intracavitary brachytherapy; Drug: Concurrent chemotherapy; Radiation: Prophylactic extended-field Irradiation

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 638
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Ke Hu; Phone Number: +86-01069155487; Email: huk@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Ke Hu, MD; Phone Number: 010-69155482; Email: huk@pumch.cn
      • Contact: Weiping Wang, PhD; Phone Number: 010-69155483; Email: jluwangweiping@163.com
  • Shanxi
    • Xi'an, Shanxi, China
      • Recruiting
      • First Affiliated Hospital Xi'an Jiaotong University
      • Contact: Zi Liu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pelvic Irradiation; Patients receive concurrent chemoradiotherapy. The CTV includes the gross tumor, cervix, uterus, parametrium, upper part of the vagina, and pelvic lymph nodes regions. The upper border of CTV is at the level of aortic bifurcation. A dose of 45-50.4Gy is delivered to CTV with IMRT.	Radiation: Pelvic irradiation; CTV covers pelvis.; Other Names: Pelvic radiotherapy; Radiation: 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.; Other Names: Brachytherapy; Drug: Concurrent chemotherapy; Cisplatin based concurrent chemotherapy, including cisplatin as a single agent or cisplatin plus Paclitaxel.; Other Names: Chemotherapy
EXPERIMENTAL: Prophylactic EFI; Patients receive concurrent chemoradiotherapy. The CTV includes the gross tumor, cervix, uterus, parametrium, upper part of the vagina, pelvic lymph nodes regions and para-aortic lymph nodes region. The upper border of CTV is at the level of renal vessels. A dose of 45-50.4Gy is delivered to CTV with IMRT.	Radiation: 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.; Other Names: Brachytherapy; Drug: Concurrent chemotherapy; Cisplatin based concurrent chemotherapy, including cisplatin as a single agent or cisplatin plus Paclitaxel.; Other Names: Chemotherapy; Radiation: Prophylactic extended-field Irradiation; CTV covers pelvis and para-aortic lymph nodes region.; Other Names: Prophylactic radiotherapy for para-aortic lymph nodes region

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival is calculated from randomization to death from any cause.	3-year
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
Para-aortic lymph nodes failure rate	The incidence of para-aortic lymph nodes failure.	3-year
Acute toxicity evaluated with CTCAE 5.0	Evaluated with CTCAE 5.0	From the start of treatment to 3 months after treatment.
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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 17, 2019
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: May 11, 2019
• First Submitted That Met QC Criteria: May 16, 2019
• First Posted (ACTUAL): May 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 23, 2022
• Last Update Submitted That Met QC Criteria: February 6, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Uterine Cervical Neoplasms; Extended-field irradiation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: PUMCH-EFI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No