Clinical trial NCT00980759: Prophylactic Irradiation of the Para-Aortic Lymph Nodes in Locally Advanced Uterine Cervical Cancer
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cervical Cancer
Keywords: Extended-field Irradiation (EFI)
Cervical cancer
Hypoxia
Carbonic anhydrase 9 (CA9)
locally advanced uterine cervical cancer
Lead sponsor: National Cancer Center, Korea
Sponsor class: OTHER_GOV
First posted: 2009-09-21
Enrollment: 312
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization of Radiotherapy field
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: 5 years
Secondary outcomes:
measure: To evaluate overall survival, toxicities and quality of life (QOL) of the patients treated by EFI compared to the control group of patients
timeFrame: 5 years
Other outcomes:
Locations:
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center, Korea
state: Gyeonggi-do
Study officials:
affiliation: National Cancer Center
name: Joo-young J Kim, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: