Clinical trial NCT03170570: the Re-irradiation of Recurrent Cervical Cancer by IMRT
Official title: A Prospective Study on the Efficacy and Safety of the Re-irradiation of Recurrent Cervical Cancer Within the Irradiated Field by Intensity Modulated Radiotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cervical Cancer
Radiation Toxicity
Recurrent Cervical Carcinoma
Keywords: recurrent cervical cancer
re-irradiation
intensity-modulated radiotherapy
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2017-05-31
Enrollment: 108
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 3 year progression free survival (PFS)
timeFrame: 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 outcomes:
measure: 3 year recurrence free survival ( RFS)
timeFrame: 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 outcomes:
measure: 3 year overall survival ( OS)
timeFrame: evaluate the response every 3 months since the completion of treatment until the death of patient up to 36 months
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University Cancer Centre
name: xinping cao, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.