NCT02805894终止1 期
A Phase I-II Dose-escalation Study of NBTXR3 Activated by EBRT or EBRT With Brachytherapy in Patients With Newly Diagnosed Unfavorable Intermediate or High Risk Prostate Adenocarcinoma Treated With Androgen Deprivation
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Nanobiotix
- 入组人数
- 5
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose and early Dose Limiting Toxicities (DLT) of NBTXR3
研究概览
简要总结
This study is a Phase 1/2 open-label involving 2 groups of patients newly diagnosed with either unfavorable intermediate risk or high risk prostate adenocarcinoma. One group will receive only EBRT and the other group will receive a Brachytherapy boost and EBRT. Both groups will receive treatment with androgen deprivation. There will be 2 consecutive steps, a dose escalation and a subsequent dose expansion part.
详细描述
This is a Phase 1/2 prospective, open-label, two cohorts, non-randomized trial consisting of two consecutive steps, a dose escalation and a subsequent dose expansion part.
PART 1 DOSE ESCALATION: subjects with newly diagnosed Unfavorable Intermediate
Risk (UIR) or High Risk (HR) prostate adenocarcinoma, will participate in a dose escalation of NBTXR3 activated by two different radiation schedules. NBTXR3 will be administered by intra-prostate injection and then activated 10 days later either by:
- EBRT delivered as 45 Gy in 25 fractions of 1.8 Gy each; to the prostate and seminal vesicles, followed by 34.2 Gy in 19 fractions to the prostate and proximal seminal vesicles, over 9-10 weeks, utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT A) or,
- Brachytherapy Boost and EBRT delivered as a single fraction of 15 Gy in one day to the prostate by High Dose Rate Brachytherapy followed by EBRT (initiated within 2-4 weeks after completion of Brachytherapy), delivered as 45 Gy in 25 fractions of 1.8 Gy to the prostate and seminal vesicles utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT B)
PART 2 DOSE EXPANSION: Two parallel cohorts of subjects, A and B, 20 subjects per cohort, will be treated at either the RD1 (Recommended Dose of NBTXR3 given as intraprostate injection and activated by EBRT) or RD2 (Recommended Dose of NBTXR3 given as intra-prostate injection and activated by Brachytherapy Boost and EBRT), as determined in the Phase I dose escalation of the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed adenocarcinoma of the prostate gland by needle core samples with assigned Gleason score
- •Subjects ADT naive or subjects who are already on ADT treatment and scheduled to receive radiation therapy for their adenocarcinoma of prostate are eligible. An 8-week course of ADT is required to be completed prior to NBTXR3 administration and initiation of radiation therapy.
- •Pelvic and para-aortic lymph nodes must be negative on CT-scan or MRI of the abdomen and pelvis performed within 12 weeks prior to enrollment into the study
- •Prostate adenocarcinoma with High Risk (HR) and Unfavorable Intermediate Risk (UIR) for recurrence classification as determined by one of the following combinations:
- •High risk (HR): subjects with one or more of the following risk factors:
- •Clinical stage: T3/T4
- •Gleason score (GS): 8-10
- •PSA > 20
- •Unfavorable Intermediate Risk (UIR): subjects with no HR features but with one or more of the following adverse risk factors:
- •At least 2 of the following 3 factors: Gleason score(GS) 3+4=7 and/or PSA 10-20 and/or T2b/c
- •Gleason score (GS) 4+3=7
- •Greater than 50% of biopsy cores positive and at least one other risk factor:
- •Gleason score (GS) 7 and/or PSA 10-20 and/or T2b/c
- •No evidence of bone metastases (M0) on bone scan within 120 days prior to registration (PET/CT is an acceptable substitute). Equivocal bone scan findings are allowed if bone CT or MRI of hot spots are negative for metastasis
- •Baseline serum PSA value performed with an FDA-approved assay within 120 days prior to registration. Study entry PSA should not be obtained within 10-day period following prostate biopsy or following initiation of hormonal therapy
- •ECOG performance status must be 0 or 1
- •Adequate function of bone marrow:
- •Hemoglobin > 100 g/L
- •Absolute Neutrophils > 1.5 x 109/L
- •Platelets > 100 x 109/L,
- •Adequate function of kidney:
- •Serum creatinine < 1.5 x ULN
- •Adequate function of liver:
- •AST ≤ 3.0 x ULN
- •ALT ≤ 3.0 x ULN
- •Total bilirubin ≤ 1.5 x ULN
- •Non-Childbearing Potential: Male subjects and their partners must meet one of the following criteria to be considered of non-childbearing potential:
- •Males have undergone sterilization with appropriately confirmed absence of sperm in the post-vasectomy ejaculate, or
- •Heterosexually active males and their partners of childbearing potential must agree or use at least 2 forms of highly effective methods of contraception, including at least 1 barrier method. Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of <1% per year when used consistently and correctly (i.e., perfect use). Contraception must include male condom or female condom used with a spermicide (i.e., foam, gel, film, cream, suppository) as well as established use of oral, injected or implanted hormonal methods of contraception, correctly placed intrauterine device or intrauterine system.
排除标准
- •Written Informed Consent not obtained, signed and dated
- •History of colorectal surgery, or repeated endoscopic examinations/interventions related to anorectal diseases or proximal urethral stricture requiring dilatation
- •Prostate size volume ≥90 cc
- •Brachytherapy with EBRT in subjects whose prostate volume is >60cc
- •Severe, active co-morbidity, defined as follows:
- •Inflammatory bowel disease, active rectal diverticulitis, Crohn's disease affecting the rectum, anal stenosis or ulcerative colitis. (Nonactive diverticulitis and Crohn's disease not affecting the rectum are allowed)
- •Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
- •Myocardial infarction within the last 6 months
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of randomization
- •Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC (Centers for Disease Control) definition
- •Prior invasive malignancy, except non-melanoma skin cancer, carcinoma in-situ of the bladder or head and neck region, unless disease free for a minimum of 2 years
- •Subjects with congenital long QT syndrome or subjects taking Class IA, Class III or Class IC anti-arrhythmic medications will require a cardiologist's evaluation prior to eligibility assessment. subjects with cardiovascular diseases can be included as long as the benefits of androgen deprivation therapy outweigh the potential risk of cardiovascular events
- •Uncontrolled lung disease
- •Subjects with any evidence of distant metastases
- •subjects with any contraindication to pelvic radiotherapy including, but not limited to, previous pelvic radiotherapy or brachytherapy
- •Presence of bilateral hip replacement prostheses
- •Hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist or oral anti-androgen) exceeding 4 months prior to registration
- •Declared high-risk for anesthesia by attending anesthesiologist, cardiologist, or other physician
- •Complete initial work up earlier than 12 weeks prior to subject registration
- •Subjects unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
- •Subjects participating in another clinical investigation at the time of signature of the informed consent.
研究组 & 干预措施
NBTXR3 activated by IMRT only
Experimental
Part I Dose Escalation
NBTXR3 will be administered by intra-prostate injection and then activated 10 days later by:
- EBRT delivered as 45 Gy in 25 fractions of 1.8 Gy each; to the prostate and seminal vesicles, followed by 34.2 Gy in 19 fractions to the prostate and proximal seminal vesicles , over 9-10 weeks, utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT A)
干预措施: NBTXR3 activated by IMRT only (Drug)
NBTXR3 activated by Brachytherapy & IMRT
Experimental
Part I Dose Escalation
NBTXR3 will be administered by intra-prostate injection and then activated 10 days later by:
- Brachytherapy Boost and EBRT delivered as a single fraction of 15 Gy in one day to the prostate by High Dose Rate Brachytherapy followed by EBRT (initiated within 2-4 weeks after completion of Brachytherapy), delivered as 45 Gy in 25 fractions of 1.8 Gy to the prostate and seminal vesicles utilizing intensity modulated radiotherapy (IMRT) with daily image guidance aligned to implanted fiducial markers (COHORT B)
干预措施: NBTXR3 activated by Brachytherapy & IMRT (Drug)
结局指标
主要结局
Maximum Tolerated Dose and early Dose Limiting Toxicities (DLT) of NBTXR3
时间窗: 24 months
Recommended Dose(s) of NBTXR3
时间窗: 24 months
次要结局
未报告次要终点
研究者
研究点 (2)
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