Prophylactic Irradiation of the Para-Aortic Lymph Nodes in Locally Advanced Uterine Cervical Cancer

• ClinicalTrials.gov Identifier: NCT00980759
• Recruitment Status: Active, not recruiting
• First Posted: September 21, 2009
• Last Update Posted: September 8, 2021
• Sponsor: National Cancer Center, Korea
• Information provided by (Responsible Party): Joo-Young Kim, National Cancer Center, Korea

Study Description

Brief Summary:

This study is an open-label, multi-institutional, randomized phase II study, which is designed to investigate the efficacy of Extended-field irradiation (EFI) on reducing recurrences at the para-aortic lymph node (PAN), and also on improving disease-free survival of locally advanced uterine cervical cancer. Radiotherapy is given as a conformal technique based on the individually taken CT scan and cisplatin is given concomitantly with radiotherapy in both EFI arm and pelvis only treatment arm. According to our past study result, patients with more hypoxic tumors are more likely to develop distant metastasis including the recurrences at PAN (1-3). This study started with examination of CA9 (hypoxia marker) expression in the primary cervical tumor before randomization because it was expected that there would be a differential benefit of EFI in patients with CA9-positive vs CA9-negative tumors. However, the study design was modified because there was too much delay in the patient with CA9-negative tumors. The patients are now registered and then immediately randomized to experimental (EFI) and control arm (pelvis only treated) with examination of CA9 expression at later time.

Condition or disease	Intervention/treatment	Phase
Cervical Cancer	Radiation: EFI; Radiation: Pelvic RT	Not Applicable

Detailed Description:

Patients with primary, untreated, histologically confirmed carcinoma of the uterine cervix are included in this study. Absence of metastatic para-aortic lymphadenopathy is the prerequisite of the enrollment, and this is confirmed by imaging studies such as MRI covering the abdomen and pelvis, and PET/CT scan. The sample size is based on the previous studies (1-3). Considering that the disease-free survival of the experimental arm (patients who are treated with prophylactic para-aortic LN irradiation) and those who are not treated is 82% vs 72% (preliminary analysis), with the alpha error of 5% and statistical power of 90% (one-sided), a total of 140 patients in each treatment arm is needed. With 10% of follow-up loss taken into account, the total number of patients will be 312. Above figures were calculated on the basis of 80% statistical power and 5% type I error rate. PAN is treated prophylactically in the experimental arm with 45Gy/25F/5week fractionation schedule. Pelvis is treated according to the individual institute's practice guideline. Boost treatment for any enlarged pelvic lymph node or residual cervical/ parametrial disease with conformal radiation technique are allowed. Intracavitary radiation is given via low-dose-rate or high-dose-rate brachytherapy technique. Weekly cisplatin is given to all patients, however, when the patient's physical condition does not allow cisplatin administration, it can be omitted. This should be taken into account in the final analysis. The stage and the presence of pelvic lymphadenopathy are two stratification factors.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 312 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomization of Radiotherapy field
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Study of Prophylactic Irradiation of the Para-Aortic Lymph Nodes by 3-D Conformal Radiotherapy Technique With Concurrent Chemotherapy Based on the Hypoxic Status of Locally Advanced Uterine Cervical Cancer
• Study Start Date: July 28, 2006
• Actual Primary Completion Date: November 30, 2019
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: EFI(Extended-Field Irradiation); Para-aortic and Pelvic Irradiation with chemotherapy(cisplatin)	Radiation: EFI; Para-aortic and Pelvic Irradiation with chemotherapy(cisplatin); Other Name: Extended-field Irradiation
Experimental: Pelvic RT; Pelvic Irradiation with chemotherapy(cisplatin)	Radiation: Pelvic RT; Only Pelvic Irradiation with chemotherapy(cisplatin); Other Name: Pelvic only treatment

Outcome Measures

Primary Outcome Measures :

1. To evaluate the efficacy of the Extended-Field Irradiation on the recurrence rate in para-aortic lymph nodes and the disease-free survival rate of the patients with locally advanced uterine cervical cancer [ Time Frame: 5 years ]

Secondary Outcome Measures :

1. To evaluate overall survival, toxicities and quality of life (QOL) of the patients treated by EFI compared to the control group of patients [ Time Frame: 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patients (who have been adequately clinically staged) with primary, untreated, histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix, FIGO stage IB1 with pelvic lymph node metastasis, IB2, IIA(≥4cm in tumor size, or pelvic LN metastasis), IIB, IIIA, IIIB with only unilateral pelvic wall extension, and IVA
2. Patients with negative, para-aortic lymphadenopathy determined by pelvic MRI and/or PET/CT scan.
3. Patients with adequate bone marrow function: ANC greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul at the beginning.
4. Patients with adequate renal function: creatinine equal to or less than 2.0 mg/dL.
5. Patients who have signed an approved informed consent and authorization
6. Patients who have met the pre-entry requirements specified in section 6.0.
7. Patients with ECOG Performance Status of 0, 1, 2 and Karnofsky Performance Scale of 100, 90, 80, 70, 60, 50
8. Age: 18≤age≤80

Exclusion Criteria:

1. Stage IIIb with bilateral pelvic wall extension and stage IVB lesions are not eligible.
2. Patients with histology other than squamous, adeno, adenosquamous cell carcinoma
3. Patients who have received prior radiotherapy of pelvis or total hysterectomy Patients who have diagnosis of other malignant tumors other than non- malignant melanoma skin cancer or stage I. II papillary, follicular thyroid cancer.

Contacts and Locations

Locations

Korea, Republic of

National Cancer Center, Korea

Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769

Sponsors and Collaborators

National Cancer Center, Korea

Investigators

• Principal Investigator: Joo-young J Kim, M.D., Ph.D.; National Cancer Center

More Information

• Responsible Party: Joo-Young Kim, Principal Investigator, National Cancer Center, Korea
• ClinicalTrials.gov Identifier: NCT00980759
• Other Study ID Numbers: NCCCTS-06-209
• First Posted: September 21, 2009
• Last Update Posted: September 8, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Joo-Young Kim, National Cancer Center, Korea:

Extended-field Irradiation (EFI); Cervical cancer; Hypoxia; Carbonic anhydrase 9 (CA9); locally advanced uterine cervical cancer

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases