the Re-irradiation of Recurrent Cervical Cancer by IMRT

A Prospective Study on the Efficacy and Safety of the Re-irradiation of Recurrent Cervical Cancer Within the Irradiated Field by Intensity Modulated Radiotherapy

this is a prospective clinical trial using intensity modulated radiotherapy（IMRT）for the treatment of cervical cancer patients with recurrent disease within the previously irradiated field. Sixty patients will be enrolled after careful selection to meet the including criteria and excluding criteria. A primary course of 36Gy will be prescribed to the recurrent site and a further 9-24Gy of dose escalation will be prescribed to the gross tumor volume in the second course according to the toxicities and the shrinkage of tumor. Weekly concurrent cisplatin of 30mg/m2 by five weeks will be administrated intravenously to the selected patients. Acute and late toxicities will be monitored and survival endpoints will be tracked with our follow-up protocol to evaluate the safety and efficacy of this approach.

Study Overview

• Status: Unknown
• Conditions: Cervical Cancer; Radiation Toxicity; Recurrent Cervical Carcinoma
• Intervention / Treatment: Device: intensity-modulated radiotherapy

Detailed Description

Introduction: Cervical cancer is the seventh most common and the eighth deadliest cancer in Chinese women. In spite of the advances in multimodality treatment regimens, there were 15-40% patients suffering from recurrence within initial irradiated field[1, 2], of which 95% recurrence occurred within 2 years and only 20% of them could be treated by salvage treatment[3-6]. there were controversies on how recurrent cervical cancer within the irradiated field should be dealt with. Surgery such as pelvic extenteration had to remove involved organs including intestine, rectum or bladder and sometimes led to severe complications and a poor quality of life. After the initial 45-50Gy irradiated to the whole pelvis, it seemed to have minimal space of further re-irradiation for recurrent disease as conventional radiotherapy was applied when considering late toxicities of organs at risk. The radiation dose for pelvic structures received will reach 45-50 Gy, almost reached the upper limits of normal tissues. For recurrent cervical cancer patients receiving retreatment by radiotherapy, the toxicity increased by 30%-56%[2] when conventional technique was applied, toxicities restricted sufficient treatments to the recurrence disease leading to a poor prognosis, which was usually less than a year [8]. IMRT has an advantage over conventional techniques because of delivering a high dose to target volume while sparing organs at risk which were previously irradiated in the primary radiotherapy. We have a five years' experience using IMRT to treat patients with recurrent disease within the previously irradiated field and most of patients showed good response and tolerable complication. According to our retrospective research (publishing), thirty-three patients made a median survival time of 14.06 months, one year overall survival was 55% and 2 year overall survival was 22%, which were better than the results of one year survival 10-20% from previous studies [8]. For further evidence, we designed this prospective clinical trial to evaluate the efficacy and safety when using intensity modulated radiotherapy to treat patients with recurrent cervical cancer within the previously irradiated field.

Methods: Sixty patients with recurrent cervical cancer within the previously irradiated field will be prospectively enrolled in this study. Only patients meeting both the including criteria and exclusion criteria will be carefully selected considering potential severe toxicities. A primary course of 36Gy will be prescribed to the recurrent site and a further 9-24Gy of dose escalation will be prescribed to the gross tumor volume in the second course according to the toxicities and the shrinkage of tumor to the irradiation. Intensity Modulated RadioTherapy (IMRT) will be chosen for dose delivery as this technique gives sufficient dose to target volume meanwhile sparing organs at risk. Weekly cisplatin of 30mg/m2 by five weeks will be administrated intravenously to the selected patients.

Outcome measurements: Toxicities will evaluated using Common Terminology Criteria for Adverse Events version 4.0 (CTCAE 4.0). Acute toxicities will be monitored weekly until one month after the completion of radiotherapy and chemotherapy. Then late toxicities will be recorded by monthly following-up. Three year's progression free survival (3y PFS) and three year's recurrence free survival(3y RFS) are the major endpoints of this study. Every three months the patients will be evaluated with necessary modalities such as physical examination, blood test, radiography, computed tomography, magnetic resonance and/or positron emission topography until three year after the last radiotherapy/chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: xinping cao, MD; Phone Number: (86)13602736388; Email: caoxp@sysucc.org.cn
• Study Contact Backup: Name: kai chen, MD; Phone Number: (86)13924254460; Email: chenkai1@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: xinping cao, MD; Phone Number: (86)13602736388; Email: caoxp@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients have provided a signed Informed Consent Form.
• Histologically confirmed cervical cancer patients after initial radiotherapy with in-field recurrence age 18-65
• Willing to have retreatment by radiotherapy
• ECOG status 0～2，Karnofsky(KPS) score ≥80
• Normal internal organ function

Exclusion Criteria:

• Having the serious cardiovascular disease or other serious complications.
• Woman in pregnancy and breast-feeding.
• Patients who had other malignant tumors in five years .
• Patients who had epilepsy.
• Patients who had infectious diseases.
• Patients who had severe side effects from previous treatment, such as intestinal disease, radiation induced pneumonia, diabetes, renal failure and hepatic failure.

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: treatment; retreatment using intensity-modulated radiotherapy for cervical cancer patients with in-field recurrence	Device: intensity-modulated radiotherapy; IMRT: intensity modulated radiotherapy, Treatment schedule: 4-7 weeks, 20-35 fractions, unless the stop indications were met, treatment will continue.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year progression free survival (PFS)	3 year progression free survival	evaluate the response every 3 months since the completion of treatment until the progression of disease or death of patient up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year recurrence free survival ( RFS)	3 year recurrence free survival	evaluate the response every 3 months since the completion of treatment until the recurrence of disease or death of patient up to 36 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
3 year overall survival ( OS)	3 year overall survival	evaluate the response every 3 months since the completion of treatment until the death of patient up to 36 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: xinping cao, MD, Sun Yat-Sen University Cancer Centre

Publications and helpful links

General Publications

• Andreu-Martinez FJ, Martinez-Mateu JM. Hypoxia and anaemia in patients with cancer of the uterine cervix. Clin Transl Oncol. 2005 Sep;7(8):323-31. doi: 10.1007/BF02716547.
• Timmer PR, Aalders JG, Bouma J. Radical surgery after preoperative intracavitary radiotherapy for Stage IB and IIA carcinoma of the uterine cervix. Gynecol Oncol. 1984 Jun;18(2):206-12. doi: 10.1016/0090-8258(84)90027-1.
• Mayr NA, Wen BC, Benda JA, Sorosky JI, Davis CS, Fuller RW, Hussey DH. Postoperative radiation therapy in clinical stage I endometrial cancer: corpus, cervical, and lower uterine segment involvement--patterns of failure. Radiology. 1995 Aug;196(2):323-8. doi: 10.1148/radiology.196.2.7617840.
• Look KY, Rocereto TF. Relapse patterns in FIGO stage IB carcinoma of the cervix. Gynecol Oncol. 1990 Jul;38(1):114-20. doi: 10.1016/0090-8258(90)90021-c.
• Potter ME, Alvarez RD, Shingleton HM, Soong SJ, Hatch KD. Early invasive cervical cancer with pelvic lymph node involvement: to complete or not to complete radical hysterectomy? Gynecol Oncol. 1990 Apr;37(1):78-81. doi: 10.1016/0090-8258(90)90312-9.
• Anthopoulos AP, Manetta A, Larson JE, Podczaski ES, Bartholomew MJ, Mortel R. Pelvic exenteration: a morbidity and mortality analysis of a seven-year experience. Gynecol Oncol. 1989 Nov;35(2):219-23. doi: 10.1016/0090-8258(89)90047-4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2016
• Primary Completion (ANTICIPATED): April 30, 2019
• Study Completion (ANTICIPATED): January 31, 2020

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: May 30, 2017
• First Posted (ACTUAL): May 31, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: recurrent cervical cancer; re-irradiation; intensity-modulated radiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Disease Attributes; Uterine Cervical Neoplasms; Recurrence
• Other Study ID Numbers: RRTCC2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No