Rapid Palliation in Locally Advanced Cervical Cancer: A Phase III Randomized Trial
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Tata Memorial Hospital
- Enrollment
- 230
- Locations
- 1
- Primary Endpoint
- Pain Relief (Numerical pain rating scale will be used)
Study Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •Moderate to Severe Pain on Numerical Rating Score (Score 4 or higher).
- •Anticipated survival < 12 months.
- •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
- •Patients with distant metastasis needing upfront systemic therapy.
- •Presence of retroviral disease
- •Non-compliant for follow up.
- •Expected survival <3 months.
Arms & Interventions
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
Intervention: Long course palliative treatment. (Radiation)
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.
Intervention: Short course palliative radiation. (Radiation)
Outcomes
Primary Outcomes
Pain Relief (Numerical pain rating scale will be used)
Time Frame: 1 week, 4 week, 7 week, 12 weeks
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
Secondary Outcomes
- Patterns of terminal event (Due to local relapse or Distant Metastasis)(By telephonic interview of the relatives at 3, 6, 9 or 12 months, as applicable)
- Late gastrointestinal and genitourinary toxicities(After 90 days of Radiotherapy)
- Overall survival, defined as time from randomization until death due to any cause.(1 year)
- Quality of Life using Cx-24 questionnaires(At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.)
- Pain Relief (Numerical pain rating scale will be used)(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)(1 week,4 week,7week,12 weeks)
- Compliance to therapy(7 week,12 week, 3 month, 9 month, 12 month)
- Acute gastrointestinal and genitourinary toxicities(Within 90 days of Radiotherapy)
- Quality of Life using EORTC QLQC30 questionnaires(At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.)
- Change in use of analgesics (WHO ladder)(12 weeks, 3 month, 9 month, 12 month)
- Quality of Life using EORTC QLQC-15 Pall questionnaires(At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.)
Investigators
Supriya Sastri (chopra)
Professor
Tata Memorial Hospital