High Dose Intensity Modulated Radiation Therapy in the Cervical Cancer With Metastatic Lymphadenopathies.

A Phase II Study of High Dose Intensity Modulated Radiation Therapy in the Cervical Cancer With Metastatic Lymphadenopathies at Initial Diagnosis.

This phase II study of high dose intensity modulated radiation therapy in the cervical cancer with metastatic lymphadenopathies at initial diagnosis

Study Overview

• Status: Unknown
• Conditions: Cervical Cancer
• Intervention / Treatment: Radiation: Tomotherapy

Detailed Description

Lymph node (LN) involvement in cervical cancer is a poor prognostic factor(1). Although lymph node evaluation is not a part of the International Federation of Gynecology and Obstetrics (FIGO) staging system(2), it is generally performed as one of the initial workup of patients with cervical cancer by use of modern imaging tools for accurate evaluation of the disease extent and possible treatment adjustment. Kidd et al reported the positron emission tomography with [18F] fluorodeoxyglucose (FDG-PET)-positive lymph node rate is 47% at diagnosis in 560 patients. They also showed that within a stage, patients with PET-positive lymph nodes had significantly worse disease specific survival than those with PET-negative lymph nodes (p<0.001)(3).

Historically, dose escalation to the pelvic or para-aortic metastatic lymphadenopathies was not given as much attention as primary uterine cervical lesion partly because of the expected increased risk of bowel toxicity with when conventional radiotherapy technique was used. Unlike for the head and neck cancer where intensity modulated radiation therapy (IMRT) or tomotherapy was actively used for treatment of large lymphadenopathies and shown to produce improved disease control(4, 5) , there are few similar studies for cervical cancer. It is well known that more than 60 Gy10 2Gy equivalent dose (EQD2, α/β=10 Gy) is needed to control the gross tumor sized of 10 mm, containing 109 cells, according to the logarithmic cell killing(6). Theoretically, pelvic and para-aortic LNs (PAN) could not be controlled with the dose of 45-50 Gy10 EQD2, and we need to escalate the dose as much as possible with new radiation technology.

In the current is study, we evaluate the LNs control rate, toxicity rate, progression-free survival and overall survival in cervical cancer patients with lymphadenopathies and treated with high dose intensity modulated radiation therapy

• Study Type: Interventional
• Enrollment (Anticipated): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center, Korea
    • Goyang-si,, Gyeonggi-do, Korea, Republic of, 411-769
      • National Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients (who have been adequately clinically staged) with primary, untreated, histologically confirmed carcinoma of the uterine cervix (including clear cell and small cell carcinoma), with metastatic lymphadenopathies (any of pelvis or PAN >1.5 cm in short diameter, with/without biopsy proven inguinal lymph node [ING])
2. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, 2
3. Patients with adequate bone marrow function: absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, platelets greater than or equal to 100,000/mcl at the beginning.
4. Patients with adequate renal function: creatinine equal to or less than 2.0 mg%.
5. Patients who have signed an approved informed consent and authorization

Exclusion Criteria:

1. Patients with recurrent LN(s) which was(were) previously irradiated.
2. Patients who have diagnosis of other malignance tumors except papillary or follicular thyroid cancer or skin cancer
3. Patients with metastatic lymphadenopathies other than pelvis, PAN, ING (e.g. supraclavicular or mediastinal metastatic lymphadenopathy)
4. Patients with distant organ metastasis (e.g. bone, lung, brain…)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tomotherapy; Tomotherapy fraction size (Gy) = 0.4 x 진단 당시의 LN short diameter (cm) + 1.6 (pilot study range, 1.5-3.0 Gy); Total dose(summation dose with 3D-CRT) (Gy10) (EQD2, α/β=10 Gy) = 5 x 진단 당시의 LN short diameter (cm) + 56 (pilot study range, 54.6-78.0 Gy)	Radiation: Tomotherapy; IMRT boost of gross LNs; Tomotherapy fraction size (Gy) = 0.4 x 진단 당시의 LN short diameter (cm) + 1.6 (pilot study range, 1.5-3.0 Gy); Total dose(summation dose with 3D-CRT) (Gy10) (EQD2, α/β=10 Gy) = 5 x 진단 당시의 LN short diameter (cm) + 56 (pilot study range, 54.6-78.0 Gy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From date of initiation of radiotherapy until the date of documented date of death from any cause, assessed up to 3 years	documented data of death, up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival (DFS)	From date of initiation of radiotherapy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.; Progression-free survival of lymph nodes(LNs) treated with high dose ② Regional LN (other than the LNs treated with high dose) failure-free survival ③ Distant organ (other than para-aortic LNs[PAN]) failure-free survival	documented date of progression or death, up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
RTOG acute and late Toxicity	① Acute: gastrointestinal (GI), genitourinary (GU), bone marrow (BM) ② Late: GI, GU, lower extremity edema, treatment-related neuropathy, bone density change	every follow-up date, up to 3 years

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Collaborators: Keimyung University Dongsan Medical Center
• Investigators: Principal Investigator: Jooyoung Kim, M.D., National Cancer Center, Korea

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 13, 2012
• Primary Completion (ANTICIPATED): July 1, 2022
• Study Completion (ANTICIPATED): July 1, 2022

Study Registration Dates

• First Submitted: October 15, 2012
• First Submitted That Met QC Criteria: November 15, 2012
• First Posted (ESTIMATE): November 21, 2012

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: cervical cancer with metastatic lymphadenopathies
• Additional Relevant MeSH Terms: Neoplasms; Lymphatic Diseases; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Lymphadenopathy
• Other Study ID Numbers: NCCCTS 12-615

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: undecided