NOX66 and Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer - a Phase 1b Proof of Concept and Dose Confirmation Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 10
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events Including SAEs [Safety and Tolerability] of NOX66 Combined With Radiation Therapy at Multiple Timepoints
研究概览
简要总结
The study is intended as a Proof of Concept and dose confirmation study. The primary objective of this study is to observe safety and tolerability of idronoxil (NOX66) in combination with radiotherapy (at palliative doses) in patients with metastatic castrate-resistant prostate cancer (CRPC) and to confirm dose in order to progress to Phase 2/3.
详细描述
This study will investigate three escalating doses of NOX66 in combination with palliative dose of radiation therapy to establish safety profile and / or obtain efficacy signals and to determine the optimal dose for future radiation therapy combination studies.
The key hypotheses to be tested in this study are:
- That NOX66 can be safely added to palliative dose radiation therapy.
- That NOX66 may sensitise tumours to palliative doses of radiation therapy
- That NOX66 in combination with radiation therapy may trigger or augment an abscopal effect
Participants will have a minimum of 1 symptomatic lesion amenable to radiation therapy.
Radiation therapy will be delivered at a 20Gy dosage over 5 fractions. NOX66 will be taken on 13 consecutive days starting 1 day prior to radiotherapy.
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
- •Provision of informed consent
- •≥ 18 years of age
- •Histologically confirmed prostate cancer and/or PSA of >100 ng/mL at original diagnosis
- •Metastatic disease evidenced by either CT/MRI imaging or bone scan
- •Objective evidence of disease progression as defined by either:
- •i. Radiographic progression of in nodal or visceral metastases and bone disease progression with 2 or more new lesions ii. Rising PSA value ≥2ng/ml in at least 3 measurements, at least 1 week apart, with castrate levels of serum testosterone.
- •Eligible to receive palliative radiation therapy for management of disease
- •At least one symptomatic lesion which is suitable for radiation therapy
- •ECOG Performance status 0-2
- •A minimum life expectancy of 24 weeks
- •Adequate bone marrow, hepatic and renal function as evidenced by:
- •Absolute neutrophil count (ANC) > 1.5 x 109/L
- •Platelet count > 100 x 109/L
- •Hemoglobin > 9.0 g/dL
- •Serum bilirubin < 1.5 x ULN
- •AST/ALT (SGOT/SGPT) < 2.5 x ULN for the reference laboratory or < 5 x ULN in the presence of liver metastases
- •Serum creatinine < 1.5 x ULN
- •Ongoing androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
- •At least 4 weeks must have elapsed prior to commencement of NOX66 treatment since prior chemotherapy, investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to ≤ NCI-CTCAE (version 4.03) Grade
- •At least 21 days must have elapsed following major surgery and any surgical incision should be completely healed.
排除标准
- •Tumour involvement of the central nervous system
- •Uncontrolled infection or systemic disease
- •Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease, angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months
- •Patients with a QTc > 470 msec on screening ECG
- •Concurrent systemic chemotherapy or biological therapy
- •Any situation where the use of suppository therapy is contra-indicated or impractical (eg. chronic diarrhoea, colostomy, ulcerative colitis).
- •Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
- •Any subject whose testosterone is not suppressed i.e. is > 0.5nmols/L
- •Any other reason which, in the opinion of the investigator, will preclude suitable participation in the study.
研究组 & 干预措施
NOX66 + Radiation treatment (combined) in cohorts 1-3
NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.
NOX66 treatment given to 3 cohorts of 4 patients as 1 of 3 doses, 400mg, 800mg and 1200 mg.
Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.
干预措施: NOX66 (Drug)
NOX66 + Radiation treatment (combined) in cohorts 1-3
NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.
NOX66 treatment given to 3 cohorts of 4 patients as 1 of 3 doses, 400mg, 800mg and 1200 mg.
Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.
干预措施: Irradiation Therapy (Radiation)
NOX66 + Radiation treatment (combined) in cohort 4
NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.
NOX66 dose will be either one of 3 doses 400mg, 800mg and 1200 mg based on interim analyses of safety data and tumour response at WEEK 6 of 3 dose cohorts of 12 total patients. The Safety Steering Committee will inform on dose for cohort expansion.
Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.
干预措施: NOX66 (Drug)
NOX66 + Radiation treatment (combined) in cohort 4
NOX66 administered on Days 1-16 and radiation treatment given on Day 2 to 9 of 2-week cycle.
NOX66 dose will be either one of 3 doses 400mg, 800mg and 1200 mg based on interim analyses of safety data and tumour response at WEEK 6 of 3 dose cohorts of 12 total patients. The Safety Steering Committee will inform on dose for cohort expansion.
Radiation treatment of 20Gy given over 5 daily fractions to selected target lesion/s for all cohorts.
干预措施: Irradiation Therapy (Radiation)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events Including SAEs [Safety and Tolerability] of NOX66 Combined With Radiation Therapy at Multiple Timepoints
时间窗: Day 2, Day 6, EOT (Day 16), Week 6, Week 12, and Week 24
Safety will be assessed through reported incidence of treatment emergent adverse events (AEs), including SAEs, dose limiting toxicities, AEs leading to withdrawal, events that are greater than CTCAE Version 4.03 Grade 2 in severity. Treatment emergent AEs are those with an onset on or after the initiation of therapy. Timepoints for AE /SAE assessment are Day 2 (start of radiation therapy treatment and one day after start of NOX66 treatment), Day 6, End of treatment (Day 16), Week 6, Week 12, and Week 24.
Assessment of ECG Results
时间窗: Baseline to End of treatment (Day 16), Week 12, and Week 24.
Mean change from Baseline in ECG intervals (msec) which are assessed at End of treatment (Day 16), Week 12, and Week 24.
Assessment of Laboratory Results
时间窗: From Baseline to End of Treatment (Day 16), Week 6, Week 12, and Week 24.
Mean change from Baseline in absolute value of safety laboratory results (haematology and biochemistry) assessed at End of Treatment (Day 16), Week 6, Week 12, and Week 24.
次要结局
- Change of Target Lesions in Participants According to RECIST 1.1 Criteria(Week 6, Week 12, and Week 24)
- Change in Overall Pain Score Using the Brief Pain Inventory - Short Form (BPI-SF)(From enrolment up to Day 16, Week 6, Week 12, and Week 24)
- Assessment of Change in Physical Appearance (Physical Exam) by Measuring HEENT, Gastrointestinal, Abdominal Status at Multiple Timepoints(From enrolment up to Day 2, End of Treatment (Day 16), Week 6, Week 12, and Week 24)
- Change of Non-Target Lesions in Participants According to RECIST 1.1 Criteria(Week 6, Week 12, and Week 24)
- Overall Response According to RECIST 1.1 Criteria(From enrolment up to Week 6, Week 12, and Week 24)
- Change in Prostate Specific Antigen (PSA) Levels(From enrolment up to Week 6, Week 12, and Week 24)
- Change of ECOG Performance Status(From enrolment up to Week 6, Week 12, and Week 24)