Tomotherapy vs Conventional Radiation for Adjuvant Pelvic RT in Ca Cervix (PARCER)

Phase III Randomized Trial of Image Guided Intensity Modulated Radiotherapy (IG-IMRT) and Conventional Radiotherapy for Late Toxicity Reduction After Postoperative Radiotherapy in Ca Cervix.

The study tests Tomtherapy based Image Guided Radiation against conventional radiation techniques for it's ability to reduce long term small bowel toxicity.

Study Overview

• Status: Completed
• Conditions: Cancer Cervix
• Intervention / Treatment: Radiation: Conventional Radiation; Radiation: Tomotherapy based IGRT

Detailed Description

Postoperative pelvic radiotherapy (+/- chemotherapy) leads to reduction in the risk of local recurrence and improves progression free survival (PFS) in patients with post-operative intermediate and high risk factors following Wertheim's hysterectomy. However, adjuvant external beam radiotherapy and vaginal cuff brachytherapy increase the risk of small bowel toxicity such that patients undergoing external beam pelvic radiotherapy and vaginal cuff brachytherapy may have 15-18% incidence of late RTOG ≥ grade II small bowel toxicity. Phase II studies using new techniques like Intensity Modulated Radiotherapy (IMRT) have reported up to 50% reduction in small bowel doses with up to 30% reduction in ≥ grade II acute toxicity. However, there is no randomized data demonstrating the benefit of highly specific and conformal techniques like image guided (IG)-IMRT in reducing radiation induced small bowel toxicity in patients with cervical cancers. The present study is being proposed to test if use of IG-IMRT with Tomotherapy is associated with reduced small bowel late toxicity

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Navi Mumbai, Maharashtra, India, 410210
      • Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre

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:

• Histopathological diagnosis of carcinoma cervix with postoperative intermediate or high risk features.
• Age >18 years.
• Planned for Wertheim's hysterectomy or has already undergone Wertheim's hysterectomy OR has undergone Simple Hysterectomy with no evidence of residual nodes on MRI/PET imaging+/- confirmatory nodal biopsy.
• No evidence of paraaortic nodal metastasis.

Exclusion Criteria:

• History of multiple previous abdominal surgeries placing patient at baseline high risk of bowel toxicity or any other medical condition with baseline bowel movement disorder.
• Rectal Polyps or extensive hemorrhoids.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional RT; Patients in this arm will receive conventional radiation with or without chemotherapy	Radiation: Conventional Radiation; Standard Pelvic Radiation 50 Gy/ 25 fractions over 5 weeks
Experimental: Tomotherapy based IGRT; Patients in this arm will receive Tomotherapy based IGRT with or without chemotherapy	Radiation: Tomotherapy based IGRT; Patients in this arm will received Tomotherapy based Image Guided Intensity Modulated Radiotherapy to a dose of 50 Gy/25 fractions/5 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late bowel toxicity ≥ Grade II	Time to event and severity of late bowel toxicity are assessed	Median follow up of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To identify small bowel dose volume characteristics that predict for ≥ Grade II late toxicity	Data on dosimetric analysis of small bowel dose in reference to volume are collected in both arms and assessed for predicting dose prescription for ≥ grade II late bowel toxcity	Median follow up of 3 years
To evaluate acute toxicity difference in two study arms using CTCAE version 3.0	Acute toxicity will be reported using CTCAE V.3.0. CTCAE forms will be filled before starting radiation, weekly during radiation treatment and on each scheduled follow-up. If any toxicity occurs at another time point additional forms will be filled to capture the same. Acute toxicity difference will be calculated between the two study arms.	Within 90 days
Preoperative functional imaging features that predict for local and distant recurrence will be identified	Images acquired pre-operatively are analysed for features that predict local and distant recurrence.	3 years after completion of accrual
To compare quality of life between Tomotherapy vs conventional radiotherapy arm using EORTC QLQ C30	Assessment is done for all enrolled patients to compare the quality of life after treatment with tomotherapy and conventional radiation . EORTC QLQC30 module will be used for evaluating QOL of patients. QOL scoring will be done as per standard recommendations outlined in EORTC QLQ C30 scoring manual. All patients will undergo QOL evaluation at baseline, after treatment and at subsequent follow-up. Scale- Not at all-1 , A little Bit-2, Quite a bit-3, very much-4. 1 will be considered as better outcome & 4 will be considered as worst outcome.	3 years from completion of accrual
To compare quality of life between Tomotherapy vs conventional radiotherapy arm using EORTC QLQ CX24	Assessment is done for all enrolled patients to compare the quality of life after treatment with tomotherapy and conventional radiation. EORTC QLQCX24 module will be used to assess disease-specific and treatment-specific aspects of QoL in patients with cervical cancer. CX24 QOL scoring will be done as per standard recommendations outlined in EORTC QLQ CX24 scoring manual. All patients will undergo QOL evaluation at baseline, after treatment and at subsequent follow-up. Scale- Not at all-1 , A little Bit-2, Quite a bit-3, very much-4. 1 will be considered as better outcome & 4 will be considered as worst outcome.	3 years from completion of accrual

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital
• Investigators: Principal Investigator: Supriya Chopra, MD,DNB, ACTREC, Tata Memorial Centre

Publications and helpful links

General Publications

• Chopra S, Engineer R, Mahantshetty U, Misra S, Phurailatpam R, Paul SN, Kannan S, Kerkar R, Maheshwari A, Shylasree Ts, Ghosh J, Gupta S, Thomas B, Singh S, Sharma S, Chilikuri S, Shrivastava SK. Protocol for a phase III randomised trial of image-guided intensity modulated radiotherapy (IG-IMRT) and conventional radiotherapy for late small bowel toxicity reduction after postoperative adjuvant radiation in Ca cervix. BMJ Open. 2012 Dec 12;2(6):e001896. doi: 10.1136/bmjopen-2012-001896. Print 2012.
• Chinnachamy AN, Chopra S, Krishnatry R, Kannan S, Thomas B, Mahantshetty U, Engineer R, Shrivastava SK. Evaluation of interobserver and interscale agreement in assessing late bowel toxicity after pelvic radiation in patients with carcinoma of the cervix. Jpn J Clin Oncol. 2013 May;43(5):508-14. doi: 10.1093/jjco/hyt028. Epub 2013 Mar 20.

Helpful Links

• Radiation (3DCRT) Versus IGIMRT for Reducing Late Bowel Toxicity in Cervical Cancer (PARCER) (NCT01279135/CTRI2012/120349): Results of Interim Analyses

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): January 31, 2020

Study Registration Dates

• First Submitted: January 18, 2011
• First Submitted That Met QC Criteria: January 18, 2011
• First Posted (Estimate): January 19, 2011

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: June 9, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: IGRT,Postoperative, Cervix, Late toxicity, Bowel
• Other Study ID Numbers: Project 803