Clinical trial NCT03110497: Single Application Brachytherapy in Cervical Cancer
Official title: A Feasibility and Safety Study of Single Application Multi-fractionated High Dose Rate (HDR) Brachytherapy in Locally Advanced Cervical Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cervical Cancer
Keywords: Cervical cancer
Image guided Brachytherapy
single application
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
First posted: 2017-04-12
Enrollment: 40
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase I/ Phase II single arm study
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate safety and feasibility of single brachytherapy application with dose delivery in multiple fractions. Study will be conducted in Phase I/II clinical trial setting with strict Image guidance protocol.This study is expected reduce treatment duration and to increase ease and acceptability of brachytherapy in patients along with significant saving of resources

Detailed description: Brachytherapy for cervical cancers has evolved a long way from the era of Manchester based point A prescription to volume-based prescription in the current era of 3 Dimensional (3D) imaging. Advancement in imaging technology and widespread availability of this technology has allowed most centers worldwide to incorporate Image guided brachytherapy as a routine part of their clinical practice.

The primary advantage of 3D image guided brachytherapy is that it allows the dose given by brachytherapy to conform to the anatomy of each individual patient while reducing the doses to organs at risk (OAR) (1). This technique has shown to improve local control rates and also reduce the rates of moderate to severe morbidity in multiple single institutional series (2-6). However, treatment related urinary and gastrointestinal late morbidity is still a significant problem with the 3 year actuarial incidence of intermediate to major morbidity (Grade≥2) being 30% and 29% for urinary and gastrointestinal side effects, respectively and Major morbidity (Grade≥3) is seen in 7% and 8%, respectively \[An intErnational study on MRI guided BRachytherapy in locally Advanced CErvical cancers (EMBRACE) study 2014, work in progress(7)\].

Most important factor determining late toxicities in radiotherapy is dose per fraction and total dose (total BEDGy3) rather than rate of dose accumulation or number of applications, which is evident from many trials of HDR brachytherapy.

The dose per fraction in the protocol of 9Gy, 7Gy and 7Gy HDR is effective in terms of local control rates and toxicities which has been published(8,9).

Our study is designed to evaluate the feasibility to deliver complete course of HDR brachytherapy in a single application while achieving dose constraints to OARs and keeping in account inter-fraction variation of doses to OAR's.

In the protocol proposed here, The Investigators intend to deliver fractionated treatments in a strict image based and quality controlled environment to minimize the doses to OAR's. Also if the constraints are not achieved, patients would be offered Standard brachytherapy regimen. This would ensure that the anticipated late toxicities would be minimized.

This study is expected to decrease overall treatment time and increase the ease and acceptability of brachytherapy in patients and with significant saving of resources while maintaining disease control rates and toxicity rates similar to standard protocols.

Eligibility criteria: Inclusion Criteria:

* Histologically diagnosed invasive cervical cancer (squamous carcinoma, adenosquamous carcinoma, adenocarcinoma)
* International Federation of Gynecology and Obstetrics (FIGO) stage 2b-4a after thorough clinical examination and work-up investigation
* Suitable for radical radiation therapy with/without chemotherapy, and also for brachytherapy boost
* Accepts the Informed consent process and signs the form on his/her will.

Exclusion Criteria:

* Patients with vesico-vaginal fistula or recto-vaginal fistula at diagnosis
* Patients at high risk of anaesthesia and patients with phobia /contra-indications to undergo MRI
* Patients not suitable for brachytherapy
* Metastatic disease beyond iliac on standard imaging
* Vault cancers/recurrence
* Previous history of pelvic radiation
* Non-compliance to treatment
* Medical or psychological illness precluding treatment protocol

Primary outcomes:
measure: Number of participants achieving specified dosimetric constraints
timeFrame: 1 year
Secondary outcomes:
measure: Number of participants with adverse events as assessed by CTCAE v 4.0
timeFrame: 2 years
measure: Local control rate
timeFrame: 2 years
measure: Percentage Inter-fraction dose variation
timeFrame: 1 year
Other outcomes:
Locations:
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
Study officials:
affiliation: Professor, Department of Radiation oncology, Tata memorial Centre, Mumbai
name: Umesh Mahantshetty, MD, DNB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tanderup K, Nielsen SK, Nyvang GB, Pedersen EM, Rohl L, Aagaard T, Fokdal L, Lindegaard JC. From point A to the sculpted pear: MR image guidance significantly improves tumour dose and sparing of organs at risk in brachytherapy of cervical cancer. Radiother Oncol. 2010 Feb;94(2):173-80. doi: 10.1016/j.radonc.2010.01.001.
citation: Lindegaard JC, Fokdal LU, Nielsen SK, Juul-Christensen J, Tanderup K. MRI-guided adaptive radiotherapy in locally advanced cervical cancer from a Nordic perspective. Acta Oncol. 2013 Oct;52(7):1510-9. doi: 10.3109/0284186X.2013.818253. Epub 2013 Aug 21.
citation: Potter R, Dimopoulos J, Georg P, Lang S, Waldhausl C, Wachter-Gerstner N, Weitmann H, Reinthaller A, Knocke TH, Wachter S, Kirisits C. Clinical impact of MRI assisted dose volume adaptation and dose escalation in brachytherapy of locally advanced cervix cancer. Radiother Oncol. 2007 May;83(2):148-55. doi: 10.1016/j.radonc.2007.04.012.
citation: Potter R, Georg P, Dimopoulos JC, Grimm M, Berger D, Nesvacil N, Georg D, Schmid MP, Reinthaller A, Sturdza A, Kirisits C. Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancer. Radiother Oncol. 2011 Jul;100(1):116-23. doi: 10.1016/j.radonc.2011.07.012. Epub 2011 Aug 5.
citation: Sturdza A, Potter R, Fokdal LU, Haie-Meder C, Tan LT, Mazeron R, Petric P, Segedin B, Jurgenliemk-Schulz IM, Nomden C, Gillham C, McArdle O, Van Limbergen E, Janssen H, Hoskin P, Lowe G, Tharavichitkul E, Villafranca E, Mahantshetty U, Georg P, Kirchheiner K, Kirisits C, Tanderup K, Lindegaard JC. Image guided brachytherapy in locally advanced cervical cancer: Improved pelvic control and survival in RetroEMBRACE, a multicenter cohort study. Radiother Oncol. 2016 Sep;120(3):428-433. doi: 10.1016/j.radonc.2016.03.011. Epub 2016 Apr 29.
citation: Fokdal L, Sturdza A, Mazeron R, Haie-Meder C, Tan LT, Gillham C, Segedin B, Jurgenliemk-Schultz I, Kirisits C, Hoskin P, Potter R, Lindegaard JC, Tanderup K. Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: Analysis from the retroEMBRACE study. Radiother Oncol. 2016 Sep;120(3):434-440. doi: 10.1016/j.radonc.2016.03.020. Epub 2016 Apr 21.
citation: Patel FD, Sharma SC, Negi PS, Ghoshal S, Gupta BD. Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys. 1994 Jan 15;28(2):335-41. doi: 10.1016/0360-3016(94)90055-8.
citation: Shrivastava S DK, Mahantshetty U, Engineer R, Patil N, Deshpande D, Tongaonkar H Comparing Low-Dose-Rate andHigh-Dose-Rate Intracavitary Brachytherapy in Carcinoma Cervix: Results From a Randomized Controlled Study. . Int J Radiat Oncol Biol Phys 2006, 1; 66.