PARCERII: Postoperative Hypofractionated Radiation in Cervical and Endometrial Tumours: Phase II Study

Sponsor

Tata Memorial Centre (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05857631

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary aim of the trial is to investigate the late effects of hypofractionated external radiation (39 Gy in 13 fractions) in patients requiring post-operative radiation for early-stage cervical and endometrial cancers.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer Endometrial Cancer	Radiation: Hypofractionated Image guided External Beam Radiation Therapy (EBRT) Drug: Cisplatin Radiation: Vaginal brachytherapy	N/A

Detailed Description

This is a phase II prospective study that will be accruing patients with post operative cervical or endometrial cancer requiring adjuvant pelvic radiation.

External beam radiotherapy (Intensity modulated radiotherapy/arc technique) will be delivered to pelvis to a dose of 39 Gray (Gy) in 13 fractions at 3 Gy per fraction, delivered once daily over 2.5 - 3 weeks. Treatment will be delivered with Intensity Modulated Radiotherapy (IMRT) under image guidance. Patients for whom concurrent chemotherapy is indicated (as per adverse risk features) will receive concurrent weekly cisplatin (40mg/m2) based on standard institutional protocol. All patients with post-operative cervical cancer will receive vaginal brachytherapy after the completion of external beam radiation. Patients with endometrial cancer with certain pre defined risk factors will also receive vaginal brachytherapy. The dose of vaginal brachytherapy will be 6 Gy high dose rate brachytherapy delivered as two different fractions, one week apart. Patients will be evaluated by the concerned investigators on a weekly basis during radiation therapy and all the toxicities will be documented according to the CTCAE V 5.0.

Patients will be followed up 3 monthly for the first 2 years, then 6 monthly from years 2 - 5, and annually thereafter. CTCAE version 5 will be used for toxicity grading at each follow-up. Quality of life assessment will be performed at baseline prior to the start of radiation and on follow-up at pre-specified times using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and Cervix - 24 (CX24) for cervical cancer patients and Endometrium 24 (EN24) for endometrial cancer patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single-arm, open-label phase II trial investigating the cumulative incidence of late grade ≥2 gastro-intestinal or genito-urinary toxicities in patients receiving adjuvant hypofractionated external beam radiotherapy to the pelvis for post-operative cervical or endometrial cancer.Single-arm, open-label phase II trial investigating the cumulative incidence of late grade ≥2 gastro-intestinal or genito-urinary toxicities in patients receiving adjuvant hypofractionated external beam radiotherapy to the pelvis for post-operative cervical or endometrial cancer.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Postoperative Hypofractionated Radiation in Cervical and Endometrial Tumours: Phase II Study

Anticipated Study Start Date :

May 25, 2023

Anticipated Primary Completion Date :

May 25, 2026

Anticipated Study Completion Date :

May 25, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hypofractionated Image guided External Beam Radiation Adjuvant hypofractionated external beam radiotherapy for post operative patients with cervical or endometrial cancer.	Radiation: Hypofractionated Image guided External Beam Radiation Therapy (EBRT) External beam radiotherapy to pelvis: Post operative hypofractionated external beam radiotherapy with intensity modulated/arc technique, to a dose of 39 Gy in 13 fractions, at 3 Gy per fraction, delivered once daily, 5 days a week, over 2.5-3 weeks. Other Names: Radiotherapy Drug: Cisplatin Patients who require adjuvant chemotherapy along with radiation, based on predefined risk features, will receive 5 cycles of cisplatin on a weekly basis with a dose of 40 mg/m2 by IV infusion over a period of 1 hour 2-4 hours prior to start of EBRT. Other Names: Chemotherapy Radiation: Vaginal brachytherapy Vaginal brachytherapy, two fractions of 6 Gy each, delivered 1 week apart. Other Names: Brachytherapy

Arm

Intervention/Treatment

Experimental: Hypofractionated Image guided External Beam Radiation

Adjuvant hypofractionated external beam radiotherapy for post operative patients with cervical or endometrial cancer.

Radiation: Hypofractionated Image guided External Beam Radiation Therapy (EBRT)

External beam radiotherapy to pelvis: Post operative hypofractionated external beam radiotherapy with intensity modulated/arc technique, to a dose of 39 Gy in 13 fractions, at 3 Gy per fraction, delivered once daily, 5 days a week, over 2.5-3 weeks.

Other Names:

Radiotherapy

Drug: Cisplatin

Patients who require adjuvant chemotherapy along with radiation, based on predefined risk features, will receive 5 cycles of cisplatin on a weekly basis with a dose of 40 mg/m2 by IV infusion over a period of 1 hour 2-4 hours prior to start of EBRT.

Other Names:

Chemotherapy

Radiation: Vaginal brachytherapy

Vaginal brachytherapy, two fractions of 6 Gy each, delivered 1 week apart.

Other Names:

Brachytherapy

Outcome Measures

Primary Outcome Measures

3-year cumulative incidence of grade ≥2 gastrointestinal or genitourinary toxicity [Median follow up of 3 years]
To evaluate the 3-year cumulative incidence of late grade ≥2 gastrointestinal or genitourinary toxicity using CTCAE version 5 scoring receiving radiation with hypo fractionation.

Secondary Outcome Measures

Pelvic Control Rate at 3 years [Median follow up of 3 years]
To report 3 year pelvic control rate (local and pelvic nodal) in patients receiving hypofractionated radiotherapy.
Disease Free Survival at 3 years [Median follow up of 3 years]
To report 3 year disease free survival in patients receiving hypo fractionated radiotherapy.
Overall Survival at 3 years [Median follow up of 3 years]
To report 3 year overall survival in patients receiving hypo fractionated radiotherapy.
Acute Toxicities Evaluation [3 months]
Acute toxicity will be reported using CTCAE V. 5.0
Assessment of Quality of Life for cervical cancer patients [Median follow up of 3 years]
To assess quality of life in using EORTC QLQ-C30 and CX24. Quality of life will be measured using the EORTC QLQ C-30. For cervical cancer, EORTC QLQ CX24 module will be used. 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.
Assessment of Quality of Life for endometrial cancer patients [Median follow up of 3 years]
To assess quality of life in using EORTC QLQ-C30 and EN24. Quality of life will be measured using the EORTC QLQ C-30. For endometrial tumours, EORTC QLQ EN24 will be used. 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.
C-MOSES scoring [Median follow up of 3 years]
To report cumulative toxicity score as assessed by C-MOSES scoring. Month and Severity Score (MOSES) will be calculated for each symptom (13 gastrointestinal and 6 genitourinary) with time weighted CTCAE toxicity, by using duration of time spent in each toxicity. Cumulative-MOSES score will be assessed for organ system (gastrointestinal and genitourinary), by summating MOSES of individual adverse event items respectively.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Histologically confirmed diagnosis of cervical cancer post hysterectomy with intermediate or high-risk features, requiring adjuvant EBRT ± concurrent chemotherapy OR histologically confirmed diagnosis of endometrial cancer post hysterectomy requiring adjuvant (chemo)radiotherapy to pelvis with/without vaginal brachytherapy.

Exclusion Criteria:

Patients with macroscopic residual disease (R+ resection) postoperatively
Patients requiring extended field radiotherapy (patients with involved para-aortic lymph nodes in cervical or endometrial cancer)
Patients treated with chemotherapy for any prior malignancy at any time
Patients treated with pelvic radiation previously
Patients with human immunodeficiency virus infection
Any preexisting medical conditions that may interfere with the assessment of genitourinary or gastrointestinal toxicity (This includes patients with irritable bowel syndrome, subacute intestinal obstruction, anal incontinence, hemorrhoids precluding analysis of gastro-intestinal toxicities, urinary incontinence, recurrent urinary tract infections)