Clinical trial NCT03997110: Palliative Radiation for Advanced Cervical Cancer
Official title: Rapid Palliation in Locally Advanced Cervical Cancer: A Phase III Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Cervical Cancer
Keywords: Cervical Cancer
Palliative treatment
Radiation Therapy
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Tata Memorial Centre
First posted: 2019-06-25
Enrollment: 230
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase III, Randomized, Active Controlled Trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pain Relief (Numerical pain rating scale will be used)
timeFrame: 1 week, 4 week, 7 week, 12 weeks
Secondary outcomes:
measure: Pain Relief (Numerical pain rating scale will be used)
timeFrame: 6 months, 9 months, 12 months
measure: Presence or absence of vaginal bleeding and/or discharge and relief in vaginal bleeding (as reported by the patient)
timeFrame: 1 week,4 week,7week,12 weeks
measure: Change in use of analgesics (WHO ladder)
timeFrame: 12 weeks, 3 month, 9 month, 12 month
measure: Compliance to therapy
timeFrame: 7 week,12 week, 3 month, 9 month, 12 month
measure: Quality of Life using EORTC QLQC30 questionnaires
timeFrame: At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.
measure: Quality of Life using EORTC QLQC-15 Pall questionnaires
timeFrame: At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.
measure: Quality of Life using Cx-24 questionnaires
timeFrame: At start of radiotherapy, 12 week and at 3, 6, 9 & 12 months follow up.
measure: Acute gastrointestinal and genitourinary toxicities
timeFrame: Within 90 days of Radiotherapy
measure: Late gastrointestinal and genitourinary toxicities
timeFrame: After 90 days of Radiotherapy
measure: Overall survival, defined as time from randomization until death due to any cause.
timeFrame: 1 year
measure: Patterns of terminal event (Due to local relapse or Distant Metastasis)
timeFrame: By telephonic interview of the relatives at 3, 6, 9 or 12 months, as applicable
Other outcomes:
Locations:
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharastra
Study officials:
affiliation: Tata Memorial Hospital
name: Supriya Sastri
role: PRINCIPAL_INVESTIGATOR
References: