Targeted Stem Cells Expressing TRAIL as a Therapy for Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 46
- 试验地点
- 1
- 主要终点
- Determination of recommended Phase II dose (RP2D) of MSCTRAIL in combination of cisplatin and pemetrexed treatment (Phase 1)
研究概览
简要总结
The aim of the study is to evaluate the safety and anti-tumour activity of MSCTRAIL in addition to chemotherapy in metastatic Non-small cell lung cancer (NSCLC) patients in a Phase I/II clinical trial.
In the phase I study, patients will receive cisplatin and pemetrexed on day one followed by MSCTRAIL cells on day 2. This constitutes one cycle of treatment. Each patient will receive 3 cycles of treatment at 21 day intervals. The aim of phase 1 is to estimate the recommended Phase II dose (RP2D) of MSCTRAIL in combination with pemetrexed/cisplatin chemotherapy.
During the phase II study patients will be randomised to either the intervention or the control arm of the study. All patients in both arms will receive cisplatin and pemetrexed on day one of treatment. Patients randomised to the intervention arm will receive the recommended dose of MSCTRAIL from Phase I on day 2 whilst those in the control arm will receive a placebo. As this is a double blind trial both patients and the clinical team will not know whether they are receiving MSCTRAIL or a placebo product. The aim of phase 2 is to assess tolerability and preliminary efficacy of MSCTRAIL in combination with pemetrexed/cisplatin chemotherapy.
详细描述
Phase 1:
A first-in-human, single-centre, accelerated, dose de-escalation design with a modified Bayesian continual reassessment method (mCRM) to estimate the recommended Phase II dose (RP2D) of MSCTRAIL in combination with pemetrexed/cisplatin chemotherapy.
The first cohort of three patients will receive cisplatin 75mg/m2 and pemetrexed 500mg/m2 on day 1 followed by the highest dose of MSCTRAIL, 4x10^8 cells, on day 2. This schedule will be repeated every 21 days until 3 cycles of treatment have been delivered. It is expected that patients will receive 4-6 cycles of cisplatin/pemetrexed in total and may continue with maintenance pemetrexed thereafter.
If there are no DLTs within the first cohort then a subsequent expansion cohort will receive the same regimen of cisplatin/pemetrexed and MSCTRAIL and data from this expansion cohort will be used to determine the recommended phase 2 dose (RP2D). Between 6 and 12 patients will be enrolled into phase I of the trial depending on the number of cohorts assessed.
Phase 2:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Prior chemotherapy, hormonal therapy, radiotherapy (including palliative radiotherapy), immunotherapy or treatment with an investigational drug for advanced NSCLC.
- •Any surgical procedure in the previous 6 weeks prior to registration/ randomisation
- •Known respiratory failure with baseline resting SpO2 <88%
- •Long term oxygen therapy
- •Severe intercurrent infection
- •Active or infected wounds
- •Yellow fever vaccination within 30 days prior to trial registration/randomisation
- •Subject has known sensitivity to any of the trial drugs to be administered during the trial.
- •Any contraindication to the administration and use of cisplatin, pemetrexed, vitamin B12 or folic acid
- •Prior malignancy other than NSCLC (except if the tumour was a non-melanoma skin tumour that has been completely excised or in situ cervix carcinoma), unless have been treated with curative intent with no evidence of disease for > 3 years
- •Evidence of symptomatic brain metastases requiring treatment
- •Myocardial infarction, or unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure [New York Heart Association > class II]) within 1 year of enrolment
- •Known inflammatory bowel disease
- •Known hepatitis B or C infection, human immunodeficiency virus (HIV)-positive patients
- •Pregnant women or those who are breast feeding
- •Other medications, severe acute/chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with trial participation or trial drug administration, or may interfere with the interpretation of trial results, and in the judgment of the investigator would make the patient inappropriate for entry into this trial
研究组 & 干预措施
Phase 1 - RP2D finding study
Phase I of the trial aims to establish the recommended MSCTRAIL dose when given in combination with cisplatin/pemetrexed chemotherapy in metastatic non-small cell lung cancer (NSCLC) patients
干预措施: MSCTRAIL (Genetic)
Phase 2 Intervention Arm
Cisplatin 75mg/m2 and Pemetrexed 500mg/m2 on day 1 followed by MSCTRAIL (at the recommended phase 2 dose) on day 2. This schedule will be repeated after 21 days for 3 cycles.
Patients will then receive a further 1-3 cycles of pemetrexed/ cisplatin alone. They may then be eligible for maintenance pemetrexed according to clinical response as directed by their Oncologist in line with local standard of care.
干预措施: MSCTRAIL (Genetic)
Phase 2 Control Arm
cisplatin 75mg/m2 and pemetrexed 500mg/m2 on day 1 and placebo on day 2. This will be repeated after 21 days for up to 3 cycles.
Patients will then receive a further 1-3 cycles of pemetrexed/ cisplatin alone. They may then be eligible for maintenance pemetrexed according to clinical response as directed by their Oncologist in line with local standard of care.
干预措施: Placebo (Drug)
结局指标
主要结局
Determination of recommended Phase II dose (RP2D) of MSCTRAIL in combination of cisplatin and pemetrexed treatment (Phase 1)
时间窗: until 21 days after the last dose of MSCTRAIL
The dose recommended for phase II (i.e. the Maximum Tolerated Dose, or MTD) will be the largest dose that has an estimated risk of causing DLT (defined as MSCTRAIL related adverse event of grade 3 or higher) equal or closest to the target level of 35% (the target toxicity level). A modified Bayesian continual reassessment method (mCRM) will be used.
Tumour response rate (Phase 2)
时间窗: 12 weeks post 1st MSCTRAIL infusion
At each visit patients will be assigned a RECIST visit response of CR, PR, SD or PD depending on the status of their disease compared to baseline and previous assessments. Objective tumour response rate is defined as the percentage of patients who have a confirmed visit response of CR or PR prior to any evidence of progression (as defined by RECIST 1.1).
次要结局
- Best Overall response (Phase 1&2)(Until end of follow up period (Phase 1: 1 year post last treatment, Phase 2: 2 years post last treatment))
- Progression free survival (Phase 1 & 2)(End of follow up period (Phase 1: 1 year post last treatment, Phase 2: 2 years post last treatment))
- Frequency of adverse events (Phase 1 & 2)(Up to 12 weeks post 1st MSCTRAIL infusion)
- Overall survival (Phase 2)(End of follow up period (2 years post last treatment))