Single Application Brachytherapy in Cervical Cancer

Cervical Cancer Clinical Trial

Official title:

A Feasibility and Safety Study of Single Application Multi-fractionated High Dose Rate (HDR) Brachytherapy in Locally Advanced Cervical Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03110497
• Other study ID #: TMH-1759
• Secondary ID: REF/2017/03/0137
• Status: Recruiting
• Phase: N/A
• Start date: September 17, 2017
• Est. completion date: April 17, 2020

Study information

• Verified date: January 2018
• Source: Tata Memorial Hospital
• Contact: Umesh Mahantshetty, MD, DNB
• Phone: 022 24177000
• Email: drumeshm[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 17, 2020
• Est. primary completion date: April 17, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Radiation:
• Single application multi-fraction brachytherapy
Single application brachytherapy procedure to deliver high dose rate fractions of 9Gy, 7Gy and 7Gy with 6-12 hours apart under strict image guidance

Locations

Country	Name	City	State
India	Tata Memorial Hospital	Mumbai	Maharashtra

Sponsors (1)

Lead Sponsor	Collaborator
Tata Memorial Hospital

Country where clinical trial is conducted

India, 

References & Publications (8)

Fokdal L, Sturdza A, Mazeron R, Haie-Meder C, Tan LT, Gillham C, Šegedin B, Jürgenliemk-Schultz I, Kirisits C, Hoskin P, Pötter 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. — View 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. — View 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. — View Citation

Pötter R, Dimopoulos J, Georg P, Lang S, Waldhäusl 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. — View Citation

Pötter 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. — View 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.

Sturdza A, Pötter R, Fokdal LU, Haie-Meder C, Tan LT, Mazeron R, Petric P, Šegedin 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. — View Citation

Tanderup K, Nielsen SK, Nyvang GB, Pedersen EM, Røhl 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants achieving specified dosimetric constraints	Number of participants achieving protocol specified dosimetric constraints will be measured, these dosimetric constraints are considered as a measure of safety. If not more than 20% of participants fail to achieve dosimetric constraints, trial will be considered feasible.	1 year
Secondary	Number of participants with adverse events as assessed by CTCAE v 4.0	To assess toxicity outcomes in terms of treatment related late Gastrointestinal (GI) / Genitourinary (GU) / Vaginal toxicities (grade 3 or more)	2 years
Secondary	Local control rate	Status of local disease at 2 years after treatment	2 years
Secondary	Percentage Inter-fraction dose variation	To evaluate inter fraction dose variation for organs at risk	1 year

External Links

•   EMBRACE Study