Relapse in Previously Irradiated Prostate Bed : a Phase I/II Study of Stereotactic Ablative Reirradiation Potentiated by Metformin
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 44
- 试验地点
- 23
- 主要终点
- For phase 1:. Select the recommended dose for SBRT (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy), in combination with Metformin
研究概览
简要总结
This phase I/II escalation dose study is assessing the efficacy of the recommended dose of stereotactic re-irradiation (SBRT) of relapses within the prostatectomy bed, potentiated by metformin
详细描述
The purpose of this escalation study is, first to select the recommended dose of re-irradiation SBRT in combination with Metformin (based on treatment toxicity monitoring) and then to estimate the efficacy of re-irradiation SBRT in combination with Metformin.
Five or six fractions, at a level of 5 or 6 Gray (Gy) per session (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy), will be delivered over a maximum of 12 days (from day 1 to day 10 or 12) to provide a total dose of 25 to 36 Gy.
Patient receive oral Metformin treatment from Day -15 and Day 75.
Patient will be followed for 5 years: patients visits will be planned at week 2; 4; 8; 12; and month M6; M9; M12; M18; M24; M36; 4 years and 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Written informed consent according to International Conference on Harmonisation (ICH)/ Good Clinical Practice (GCP) regulations before registration and prior to any trial specific procedures.
- •Biochemical recurrence occurring at least 2 years after external radiotherapy to the prostate lodge and the end of hormone therapy, for prostatic adenocarcinoma previously treated by radical prostatectomy.
- •Local recurrence in irradiated areas proven by biological (PSA > 0.2 ng/ml and ascending confirmed by at least 2 successive assays) and radiological (lesion visible on MRI and/or Choline PET and/or Prostate-Specific Membrane Antigen (PSMA) PET).
- •Recurrence without rectal invasion
- •Pelvic and prostate MRI evaluation
- •Absence of pelvic lymph node or metastatic recurrence proven by choline PET or PSMA PET scan
- •World Health Organisation (WHO) performance status 0-1
- •Low risk, intermediate risk and high risk with a single risk factor
- •PSA doubling time > 6 months
- •No anti-cancer treatments planned for the current relapse, including hormone therapy.
- •Age > 18 years old.
- •Life expectancy greater than or equal to 5 years.
- •Patient registered with a health insurance system.
- •Patients willing and able to comply with the planned visits, treatment plan, laboratory tests and other study procedures indicated in the protocol.
排除标准
- •Metastatic disease (bone, lymph node or other)
- •Late radiotherapy urinary or gastrointestinal toxicity (grade ≥ 2) (after radiotherapy of prostate lodge)
- •History of cancer in the 5 years prior to trial entry other than cutaneous basal cell carcinoma
- •Inflammatory bowel disease
- •Contraindications for performing MRI
- •Rectal surgery history
- •Patient treated for Diabetes
- •Creatinine clearance < 45 mL/min
- •Treatment with metformin in the last 3 months prior to inclusion
- •Severe comorbidity that may affect treatment, for example :
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of inclusion.
- •Unstable angina, myocardial infarction and/or congestive heart failure requiring hospitalization within the last 6 months
- •Myocardial infarction in the last 6 months.
- •Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) or other respiratory conditions requiring hospitalization or preventing metformin therapy at the time of inclusion.
- •Any condition associated with an increased risk of lactic acidosis (e.g., alcohol abuse, New York Heart Association (NYHA) III or IV congestive heart failure).
- •Clinically significant history of hepatopathy with Child-Pugh B or C score, including viral infection or hepatitis, alcohol abuse or cirrhosis.
- •Any acute or chronic condition that may result in tissue hypoxia (e.g. heart or respiratory failure, shock).
- •Bilateral hip prosthesis
- •Treatment with any investigational drug or participation in a clinical trial within 30 days prior to inclusion.
- •Known hypersensitivity to metformin or any of its components
- •Inability or reluctance to swallow oral medications
- •Persons deprived of liberty, under a measure of safeguard of justice, under guardianship or under the tutor authority
- •Inability to undergo medical monitoring of the trial for geographical, social or psychological reasons.
研究组 & 干预措施
Metformin + SBRT at total dose of 30 Gray (Gy)
Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)
Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 6 Gy, (day 0 to day 10)
干预措施: Metformin (Drug)
Metformin + SBRT at total dose of 36 Gy
Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)
Stereotactic Body Radiation Therapy (SBRT): Dose escalation 6 x 6 Gy (day 0 to day 12)
干预措施: Metformin (Drug)
Metformin + SBRT at total dose of 25 Gy
Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)
Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 5 Gy (day 0 to day 10)
干预措施: Metformin (Drug)
Metformin + SBRT at total dose of 36 Gy
Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)
Stereotactic Body Radiation Therapy (SBRT): Dose escalation 6 x 6 Gy (day 0 to day 12)
干预措施: Stereotactic Body Radiation Therapy (SBRT) 36 Gy (Radiation)
Metformin + SBRT at total dose of 25 Gy
Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)
Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 5 Gy (day 0 to day 10)
干预措施: Stereotactic Body Radiation Therapy (SBRT) 25 Gy (Radiation)
Metformin + SBRT at total dose of 30 Gray (Gy)
Metformin: 850 mg per day (day -15 to day 0) 1700 mg per day (day 1 to day 75)
Stereotactic Body Radiation Therapy (SBRT): Dose escalation 5 x 6 Gy, (day 0 to day 10)
干预措施: Stereotactic Body Radiation Therapy (SBRT) 30 Gray (Gy) (Radiation)
结局指标
主要结局
For phase 1:. Select the recommended dose for SBRT (either 5 x 6 Gy, 6 x 6 Gy, or 5 x 5 Gy), in combination with Metformin
时间窗: 12 weeks
SBRT toxicity will be reported during the 12 weeks following the initiation of SBRT.
For phase 2: estimate the efficacy of re-irradiation SBRT in combination with Metformin in terms of biochemical relapse-free survival rate.
时间窗: 3 years
PSA levels will be assessed every 3 months within 3 years after SBRT.
次要结局
- Estimate the efficacy of re-irradiation SBRT in combination with Metformin in terms of biochemical relapse-free survival and biochemical response(5 years)
- Estimation of the efficacy of SBRT re-irradiation in combination with Metformin in terms of progression-free survival and overall survival(5 years)
- Evaluation of acute and late genitourinary and gastrointestinal toxicities of the SBRT re-irradiation(5 years)
- Evaluation of urinary symptoms(5 years)
- Evaluation of erectile function(5 years)
- Evaluation of Quality of life after SBRT re-irradiation in combination with Metformin(5 years)