Clinical trial NCT03955367: Pelvic RT Versus Prophylactic Extended-field RT in Patients With Cervical Cancer
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Uterine Cervical Neoplasms
Keywords: Uterine Cervical Neoplasms
Extended-field irradiation
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Peking University First Hospital
name: Cangzhou Central Hospital
name: The Second Affiliated Hospital of Dalian Medical University
name: Gansu Wuwei Tumor Hospital
name: First Affiliated Hospital of Guangxi Medical University
name: Harbin Medical University Third Affiliated Hospital
name: Wuhan Union Hospital, China
name: First Affiliated Hospital of Chongqing Medical University
name: Guizhou Provincial People's Hospital
name: Second Hospital of Jilin University
name: China-Japan Union Hospital, Jilin University
name: Jilin Provincial Tumor Hospital
name: Jiangsu Cancer Institute & Hospital
name: 940 Hospital of the People's Liberation Army Joint Logistic Support Force
name: General Hospital of Benxi Iron & Steel Industry Group
name: The Affiliated Hospital of Inner Mongolia Medical University
name: General Hospital of Ningxia Medical University
name: Beijing Obstetrics and Gynecology Hospital
name: Tangshan People's Hospital
name: Zhongnan Hospital
name: Second Affiliated Hospital of Xi'an Jiaotong University
name: First Affiliated Hospital Xi'an Jiaotong University
name: The Affiliated Tumor Hospital of Xinjiang Medical University
name: Zhejiang Cancer Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Affiliated Cancer Hospital of Zhengzhou University
name: Seventh Medical Center of PLA Army General Hospital
name: Shengjing Hospital
name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Xiangya Hospital of Central South University
name: Henan Provincial People's Hospital
name: Xi'an Gaoxin Hospital
name: West China Second University Hospital
name: The Forth Affiliated Hospital of Guangxi Medical University
First posted: 2019-05-20
Enrollment: 638
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 3-year
Secondary outcomes:
measure: Overall survival
timeFrame: 3-year
measure: Distant failure-free survival
timeFrame: 3-year
measure: Para-aortic lymph nodes failure rate
timeFrame: 3-year
measure: Acute toxicity evaluated with CTCAE 5.0
timeFrame: From the start of treatment to 3 months after treatment.
measure: Late toxicity evaluated with Radiation Therapy Oncology Group (RTOG)/EORTC late radiation morbidity scoring scheme
timeFrame: 3-year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Xi'an
country: China
facility: First Affiliated Hospital Xi'an Jiaotong University
state: Shanxi
Study officials:
affiliation: Peking Union Medical College Hospital
name: Ke Hu
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.