A Phase III Randomized Clinical Trial to Study the Radiosensitizing Effect of Nelfinavir in Locally Advanced Carcinoma of Uterine Cervix.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 348
- 试验地点
- 1
- 主要终点
- Improvement in 3 year disease free survival
研究概览
简要总结
The primary aim of the trial is to study the impact of nelfinavir on 3 year disease free survival in patients with advanced carcinoma of cervix receiving standard chemoradiation (Cisplatin and Radiotherapy).
There will be two study groups. One group will receive standard treatment (concurrent chemoradiation and brachytherapy) & other group will receive nelfinavir 5-7 days prior to standard treatment (chemoradiation & brachytherapy).
详细描述
The trial is a single centre open label randomized unblinded phase-III study to evaluate the efficacy of an investigational drug (Nelfinavir) in combination with standard therapy consisting of weekly cisplatin and pelvic EBRT in cohort of patients diagnosed with FIGO 2018 stage III Carcinoma cervix.
Patient registration / randomization procedure
348 Patients will be accrued from the Gynaec Oncology Service of Tata Memorial Centre, Mumbai. A study coordinator at TMC will coordinate the accrual and study process and ensure prompt accrual and proper documentation. Eligibility will be checked based on the selection criteria and written informed consent will be obtained prior to randomization. Patients will be given appropriate time to decide for participation. Randomization will be based on a chart prepared with the help of software using a random sorting algorithm. A screening log will be maintained and include the details of all patients screened.
There are two study arms. In Experimental arm (Nelfinavir arm) 174 patients will be accrued & in Control arm (Standard Arm) 174 patients will be accrued.
If patient is randomized to standard arm patient will receive concurrent chemoradiation and brachytherapy. If patient is randomized to nelfinavir arm then nelfinavir will be started at the dose of 1250 mg bid 5-7 days prior to standard treatment (chemoradiation & brachytherapy)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •ECOG 0 to 2
- •FIGO 2018 Stage IIIA (TNM stage T3a N0 M0) FIGO 2018 Stage IIIB (TNM stage T3b N0 M0) FIGO 2018 Stage IIIC (TNM stage Any T N1 M0)
- •No previous irradiation to the pelvis or chemotherapy
- •Age 18 years and above
- •Ability to tolerate full course of pelvic radiotherapy and brachytherapy
- •Adequate bone marrow, liver, and kidney function defined as neutrophil count ≥ 1500 platelet count ≥ 100,000, total bilirubin less than 1.5 x upper limit of normal (ULN), AST and ALT ≤ 2.5 x ULN, and creatinine less than 1.5 upper limit of normal or Creatinine clearance greater than 60 mL/min/1.73 m2
- •No recent (less than 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction)
- •Ability to understand and the willingness to sign an informed consent document
- •Should be willing to undergo extra biopsy and blood collection for pharmacokinetic studies
排除标准
- •Patients with newly diagnosed diabetes , uncontrolled DM (patient with HbA1c of > 6.5% or FBS value or BSF>=126 mg/dL respectively on primary evaluation)
- •Pts on any drugs which has pharmacological interaction with nelfinavir:
- •Terfenadine, cisapride, sildenafil, lovastatin or simvastatin and medication that are metabolized by the CYP3A4 isoenzyme.
- •Antiarrhythmics (amiodarone, quinidine).
- •Neuroleptics (pimozide).
- •Sedative/Hypnotic agents (midazolam, triazolam).
- •Ergot derivatives.
- •HMG-CoA reductase inhibitors (atorvastatin).
- •Rifampicin, Rifabutin.
- •Felodipine, Nifedipine.
- •Pregnant or lactating
- •Active co existing malignancy.
- •HIV positive patients will be excluded.
- •Patients with hemophilia.
- •Patients with reduced creatinine clearance ( less than 50 ml/ min) or unilateral or bilateral hydronephrosis will be excluded.
- •History of psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
研究组 & 干预措施
Nelfinavir Arm
If patient is randomized to nelfinavir arm then nelfinavir will be given orally with food at the dose of 1250 mg bid 5-7 days prior to start of chemoradiation.
Then Pelvic EBRT (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 & ICRT 7Gy X4 # will be given.
干预措施: Nelfinavir (Drug)
Nelfinavir Arm
If patient is randomized to nelfinavir arm then nelfinavir will be given orally with food at the dose of 1250 mg bid 5-7 days prior to start of chemoradiation.
Then Pelvic EBRT (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 & ICRT 7Gy X4 # will be given.
干预措施: Cisplatin (Drug)
Nelfinavir Arm
If patient is randomized to nelfinavir arm then nelfinavir will be given orally with food at the dose of 1250 mg bid 5-7 days prior to start of chemoradiation.
Then Pelvic EBRT (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 & ICRT 7Gy X4 # will be given.
干预措施: Pelvic EBRT and Brachytherapy (Radiation)
Standard Arm
If patient is randomized to standard arm (Cisplatin +Pelvic EBRT and Brachytherapy).
In this patient will receive Pelvic EBRT (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 & ICRT 7Gy X4 #
干预措施: Cisplatin (Drug)
Standard Arm
If patient is randomized to standard arm (Cisplatin +Pelvic EBRT and Brachytherapy).
In this patient will receive Pelvic EBRT (45-50 Gy/23-25 #/5weeks) + Weekly cisplatin 40mg/m2 & ICRT 7Gy X4 #
干预措施: Pelvic EBRT and Brachytherapy (Radiation)
结局指标
主要结局
Improvement in 3 year disease free survival
时间窗: 3 years
Improvement in 3 year disease free survival by the addition of Nelfinavir to patients with advanced carcinoma of cervix and receiving standard chemoradiation (Cisplatin and Radiotherapy).
次要结局
- Change in locoregional control rates at 3 years(3 years)
- Overall survival at 5 years(5 years)
- Incidence of grade 3/4 adverse events(5 years)
- Changes in Akt levels in the tumor(5 years)
- Change in tumour hypoxia using multifunctional PET/ MRI.(5 years)
- Interindividual variability of Volume of distribution(5 years)
- Interindividual variability of Clearance of nelfinavir.(5 years)
- Interindividual variability of Clearence of Nelfinavir(5 years)
研究者
Supriya Sastri (chopra)
Principal Investigator
Tata Memorial Hospital