Palliative Radiation for Advanced Cervical Cancer (RAPPAL)

Rapid Palliation in Locally Advanced Cervical Cancer: A Phase III Randomized Trial

The present study is proposed to compare a rapid fractionation schedule of 1 week compared to a protracted schedule of 6-8 weeks for palliation for locally advanced cervical cancer.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Radiation: Long course palliative treatment.; Radiation: Short course palliative radiation.

Detailed Description

This is a prospective randomised open label Phase III study. This study is is proposed to compare a rapid fractionation schedule of 1 week compared to a protracted schedule of 6-8 weeks for palliation for locally advanced cervical cancer. The primary objective of the study is pain relief in the experimental arm as compared to the control arm from treatment until 12 weeks from start of radiotherapy. Patients with locally advanced cervical cancer (Stage III B-IV A) deemed unsuitable for full course radical pelvic radiotherapy or chemoradiation, patients whose anticipated survival is less than 12 months will be included in the study. Patients with distant metastasis and those with retroviral disease will be excluded from the study. The patients will be randomised in one of the two groups:

Arm A : Control Arm - Long Course Palliative Radiation: Week 1: All the patients will receive external sitting of radiation treatment, first fraction of 10 Gy. Week 4: All the patients will receive external sitting of radiation treatment, second fraction of 10 Gy. Week 7: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#.The patients which will be found unsuitable for brachytherapy will receive another sitting of external radiation, third fraction of 10 Gy. Week 12: After treatment completion response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/ no • Vaginal discharge- yes/no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity.

Arm B: Experimental arm- Short Course Palliative radiation. Week 1: Patients will be treated with short course radiotherapy (25Gy/5#). The dose fractionation of 25 Gy in 5# over a week will be used. Week 4: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#. The patients who will be found unsuitable for brachytherapy will be kept under observation. Week 12: After treatment completion response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/no • Vaginal discharge- yes/ no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity. Follow up: Patients follow up will be utilizing standard of care imaging and lab investigations used for the patients. Patients will be evaluated every 3 months for the study duration.There is no potential direct benefit to the study participants. However the aim is to use the available information to evolve treatment in future. The variables to be estimated are pain relief, disease related symptoms relief, CTCAE Toxicity, Quality of Life,overall survival and compliance to therapy.

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Supriya Chopra; Phone Number: 5113 02227405000; Email: supriyasastri@gmail.com
• Study Contact Backup: Name: TMH Gyn DMG TMC; Phone Number: 6038 02224177000; Email: gwg.tmc@gmail.com

Study Locations

• India
  • Maharastra
    • Mumbai, Maharastra, India, 400012
      • Recruiting
      • Tata Memorial Hospital
      • Principal Investigator: Supriya Sastri

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Locally advanced cervical cancer (Stage IIIB-IVA) deemed unsuitable for full course radical pelvic radiotherapy or chemoradiation due to the following reasons:

   • Very large volume hard fixed disease infiltrating pelvic wall muscles and ligaments on clinical examination also classified clinically as "frozen pelvis" wherein curative intent treatment is not envisaged or feasible.
   • Fistulous communication between tumour growth and rectum and bladder >2x2 cm in size (as judged by cystoscopy for bladder infiltration or clinical or proctosigmoidoscopy examination for rectal/sigmoid infiltration) wherein radical intent treatment is not intended or feasible and patient is not a candidate for pelvic exenteration.
   • Deranged renal parameters as measured by Serum Creatinine >3 mg/dl wherein diversion nephrostomy is not planned by the multidisciplinary team due to anticipated poor clinical outcomes.Furthermore concurrence for palliative intent radiotherapy should be corroborated by 2 staff radiation oncologists.
2. Moderate to Severe Pain on Numerical Rating Score (Score 4 or higher).
3. Anticipated survival < 12 months.
4. Patients with stage IVB with local disease extent as described in section 1 but systemic chemotherapy is not possible either due to deranged renal function or anticipated poor tolerance.

Exclusion Criteria:

1. Patients with distant metastasis needing upfront systemic therapy.
2. Presence of retroviral disease
3. Non-compliant for follow up.
4. Expected survival <3 months.

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: Arm A Or Control Arm- Long course palliative treatment.; Week1: All the patients will receive external sitting of radiation treatment, first fraction of 10 Gy. Week4: All the patients will receive external sitting of radiation treatment, second fraction of 10 Gy. Week7: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#.The patients who will be found unsuitable for brachytherapy will receive another sitting of external radiation, third fraction of 10 Gy. Week 12: After treatment completion response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/ no • Vaginal discharge- yes/no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity	Radiation: Long course palliative treatment.; Week1: All the patients will receive external sitting of radiation treatment, first fraction of 10 Gy. Week4: All the patients will receive external sitting of radiation treatment, second fraction of 10 Gy. Week7: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#.The patients who will be found unsuitable for brachytherapy will receive another sitting of external radiation, third fraction of 10 Gy. Week 12: After treatment completion response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/ no • Vaginal discharge- yes/no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity
Experimental: Arm B or Experimental Arm-Short course palliative radiation.; Week 1: Patients in the experimental arm will be treated with short course radiotherapy (25Gy/5#). The dose fractionation of 25 Gy in 5# over a week will be used. Week 4: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#. The patients who will be found unsuitable for brachytherapy will be kept under observation. Week 12: After treatment completion, response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/no • Vaginal discharge- yes/ no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity. Follow up: Patients follow up will be utilizing standard of care imaging and lab investigations used for the patients. Patients will be evaluated every 3 months for the study duration.	Radiation: Short course palliative radiation.; Week 1: Patients in the experimental arm will be treated with short course radiotherapy (25Gy/5#). The dose fractionation of 25 Gy in 5# over a week will be used. Week 4: Patients who have almost complete clinical response will be evaluated for brachytherapy will receive the appropriate brachytherapy procedure depending on the tumor response to a dose of 6-8Gy x 2-3#. The patients who will be found unsuitable for brachytherapy will be kept under observation. Week 12: After treatment completion, response assessment will be done using following parameters: • Pain assessment using numerical pain rating scale on 0-10 • Vaginal bleeding- yes/no • Vaginal discharge- yes/ no • Analgesic use- WHO ladder and dosing • QOL QC30, QLQC15 Pall, QLQC Cervix 24 • Disease response • Acute toxicity. Follow up: Patients follow up will be utilizing standard of care imaging and lab investigations used for the patients. Patients will be evaluated every 3 months for the study duration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Relief (Numerical pain rating scale will be used)	Pain relief in the experimental arm as compared to the control arm from treatment until 12 weeks from start of radiotherapy will be assessed. Pain relief will be assessed at 12 weeks from start of radiotherapy. (Pain has been chosen as the primary endpoint as it is the primary complaint in almost 2/3 rd of patients. Numerical pain rating scale has been chosen for objective pain assessment as it is easy to use and has been proven to be a reliable tool in multiple studies. Pain score will be documented on 11-scale numerical pain rating scale (NRS) and qualified into one of the following categories: i)Pain score of 0-3- No to mild pain ii)Pain score 4-7- Moderate pain iii)Pain score >7- Severe pain	1 week, 4 week, 7 week, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Relief (Numerical pain rating scale will be used)	Pain relief at 6, 9 and 12 month of follow up. Pain score will be documented on 11-scale numerical pain rating scale (NRS) and qualified into one of the following categories: i) Pain score of 0-3- No to mild pain ii) Pain score 4-7- Moderate pain iii) Pain score >7- Severe pain	6 months, 9 months, 12 months
Presence or absence of vaginal bleeding and/or discharge and relief in vaginal bleeding (as reported by the patient)	Complete relief in vaginal bleeding and non-infectious discharge will be documented at 12 weeks from start of RT as reported by the patient. Although vaginal bleeding and discharge are also major presenting complaints, there is no standardized objective scale or criteria for measuring these in cancer patients. Vaginal discharge if present will be qualified as infectious or non-infectious. Infectious vaginal discharge will warrant antibiotic treatment.	1 week,4 week,7week,12 weeks
Change in use of analgesics (WHO ladder)	Change in use of analgesics by either dose adjustment or stepping up/down on the WHO ladder at 12 weeks.This will also be recorded at each clinical follow up.	12 weeks, 3 month, 9 month, 12 month
Compliance to therapy	Response of local disease will be assessed clinically at end of treatment and on every follow up. Response to RT will be determined on follow-up at 7 and 12 weeks in both the arms and phone call interviews when necessary for completeness in patients with poor compliance to follow up.	7 week,12 week, 3 month, 9 month, 12 month
Quality of Life using EORTC QLQC30 questionnaires	Quality of Life using EORTC QLQC 30 questionnaire (European Organisation for Research & Treatment of Cancer - Quality of Life Questionnaire of Cancer patients) will be evaluated at start of radiotherapy and at week 12, 3 month, 6 month, 9 month,12 months 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.	At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.
Quality of Life using EORTC QLQC-15 Pall questionnaires	Quality of Life using EORTC QLQC-15 Pall (European Organisation for Research & Treatment of Cancer - Quality of Life Questionnaire in Palliative Cancer care patients) will be evaluated at start of radiotherapy and at week 12, 3 month, 6 month, 9 month,12 months 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.	At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.
Quality of Life using Cx-24 questionnaires	Quality of Life using Cx-24 questionnaires (European Organisation for Research & Treatment of Cancer - Quality of Life Questionnaire of Cervical cancer patients) will be evaluated at start of radiotherapy and at week 12, 3 month, 6 month, 9 month,12 months 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.	At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.
Acute gastrointestinal and genitourinary toxicities	Acute gastrointestinal and genitourinary toxicities using CTCAE ver4.0 grading will be measured within 90 days of Radiotherapy.	Within 90 days of Radiotherapy
Late gastrointestinal and genitourinary toxicities	Late gastrointestinal and genitourinary toxicities using CTCAE 4.0 grading will be measured after 90 days of Radiotherapy.	After 90 days of Radiotherapy
Overall survival, defined as time from randomization until death due to any cause.	Overall survival, defined as time from randomization until death due to any cause.	1 year
Patterns of terminal event (Due to local relapse or Distant Metastasis)	Events leading to death will be determined by telephonic interview of the relatives at 3, 6, 9 or 12 months, as applicable to find out the terminal cause of death.	By telephonic interview of the relatives at 3, 6, 9 or 12 months, as applicable

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital
• Collaborators: Tata Memorial Centre
• Investigators: Principal Investigator: Supriya Sastri, Tata Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2020
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: June 22, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cervical Cancer; Radiation Therapy; Palliative treatment
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms
• Other Study ID Numbers: TMH IRB 3157

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No