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

Phase 3

Recruiting

• Conditions: Uterine Cervical Neoplasms
• Interventions: Radiation: Prophylactic extended-field Irradiation; Radiation: Pelvic irradiation; Radiation: Intracavitary brachytherapy; Drug: Concurrent chemotherapy

• Registration Number: NCT03955367
• Lead Sponsor: Peking Union Medical College Hospital

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.

Study Timeline

• Study First Submitted: 2019-05-11
• Study First Submitted QC: 2019-05-16
• Study First Posted: 2019-05-20
• Study Start: 2019-06-17
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-06
• Last Update Posted: 2022-02-23
• Primary Completion: 2022-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 638

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pelvic Irradiation	Intracavitary brachytherapy	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.
Prophylactic EFI	Prophylactic extended-field Irradiation	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.
Prophylactic EFI	Concurrent chemotherapy	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.
Pelvic Irradiation	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.
Prophylactic EFI	Intracavitary brachytherapy	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.
Pelvic Irradiation	Concurrent chemotherapy	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.

Primary Outcome Measures

Name	Time	Method
Progression-free survival	3-year	Progression-free survival is defined as the time from randomization to disease progression or death from any cause, whichever is first.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

First Affiliated Hospital Xi'an Jiaotong University; 🇨🇳 Xi'an, Shanxi, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China