The Borealis-2 Clinical Trial: A Randomized Phase 2 Study Comparing Docetaxel Alone to Docetaxel in Combination With OGX-427 in Patients With Relapsed or Refractory Metastatic Urothelial Carcinoma After Receiving a Platinum-containing Regimen: Hoosier Cancer Research Network GU12-160
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 200
- 试验地点
- 35
- 主要终点
- Overall Survival
研究概览
简要总结
This is a randomized, open-label Phase 2 clinical trial to evaluate whether suppression of Hsp27 (Heat shock protein 27) production using OGX-427, a second-generation antisense oligonucleotide (ASO), in combination with docetaxel can prolong survival time compared to docetaxel alone in participants with locally advanced or metastatic urothelial carcinoma (UC) that are relapsed or refractory after receiving a platinum-containing regimen.
详细描述
OUTLINE: This is a multi-center study.
Eligible patients will be stratified based on time from prior systemic chemotherapy (< 3 vs ≥ 3 months) and Bellmunt prognostic factors criteria, which include Eastern Cooperative Oncology Group (ECOG) performance status >0, hemoglobin <10g/dL, and presence of liver metastases (0 versus 1-3 risk factors). Within the strata, participants will be randomly assigned with equal probability to either the investigational arm (Arm A: docetaxel + OGX-427) or the control arm (Arm B: docetaxel alone).
INVESTIGATIONAL ARM OGX-427 + DOCETAXEL (Arm A):
LOADING DOSE PERIOD:
Participants randomized onto the investigational arm (Arm A) will receive OGX-427 beginning with a loading dose period prior to the initiation of docetaxel treatment. The first dose of OGX-427 for the loading dose period must be administered within 5 working days of registration and randomization.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have histologically documented metastatic or locally inoperable advanced urothelial carcinoma (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3, or M1 disease. NOTE: Aberrant differentiation such as squamous, glandular (adenocarcinoma), and micropapillary are eligible unless the tumor is considered a pure histological variant according to the pathology report. Participants with small cell histology are not eligible.
- •Participants must have measurable disease defined as at least one target lesion that has not been irradiated and can be accurately measured in at least one dimension by RECIST v1.1 criteria.
- •Participants must have received prior systemic chemotherapy treatment for metastatic urothelial carcinoma. NOTE: Up to 2 prior systemic chemotherapeutic regimens given in the metastatic disease setting for urothelial carcinoma are allowed.
- •Specifically, subjects must meet one or more of the following criteria:
- •Progression during or after treatment with a regimen that includes a platinum salt (e.g., carboplatin or cisplatin) OR
- •Disease recurrence within one year after neoadjuvant or adjuvant platinum-based systemic chemotherapy, measured from the date of last dose of chemotherapy or surgery until the day the informed consent is signed
- •Participants must be ≥18 years since no dosing or adverse event data are currently available on the use of OGX-427 in participants <18 years of age.
- •Minimum of 21 days have elapsed since prior major surgery, with recovery from any adverse events.
- •Minimum of 14 days have elapsed since any prior radiation therapy, with recovery from any adverse events.
- •The effects of OGX-427 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •History of treatment with docetaxel in any setting. Participants treated with prior paclitaxel are eligible.
- •Prior enrollment in the OncoGenex Phase 2 Study OGX-427-
- •Participants may not be receiving other investigational agents.
- •Participants with known brain or spinal cord metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. NOTE: Brain imaging is not required unless the patient has symptoms or physical signs of central nervous system (CNS) disease.
- •History of allergic reactions or severe hypersensitivity reactions to drugs formulated with polysorbate 80 or antisense oligonucleotides.
- •Peripheral neuropathy ≥Grade
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
- •Cerebrovascular accident or pulmonary embolus within 3 months of randomization.
- •Pregnant women and breast feeding women are excluded from this study because of the risk to a fetus due to docetaxel chemotherapy and OGX-427 systemic treatment (fertility toxicology studies have not been completed for OGX-427).
- •Active second malignancy (except non-melanomatous skin cancer or incidental prostate cancer found on cystectomy): active secondary malignancy is defined as a current need for cancer therapy or a high possibility (>30%) of recurrence during the study.
研究组 & 干预措施
Experimental Arm: Arm A
Three doses of 600 mg OGX-427 will be administered IV during the loading dose period (days -9 to -1). Following completion of the loading dose period, 600 mg OGX-427 will be given IV weekly on days 1, 8, and 15 of each 21-day cycle.
干预措施: OGX-427 (Drug)
Experimental Arm: Arm A
Three doses of 600 mg OGX-427 will be administered IV during the loading dose period (days -9 to -1). Following completion of the loading dose period, 600 mg OGX-427 will be given IV weekly on days 1, 8, and 15 of each 21-day cycle.
干预措施: Docetaxel (Drug)
Control Arm: Arm B
Docetaxel (75 mg/M2) will be administered IV on day 1 of each 21 day cycle for a maximum of 10 cycles.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Overall Survival
时间窗: 36 Months
To determine whether docetaxel administered in combination with OGX-427 provides a survival benefit compared to docetaxel alone.
次要结局
- Safety and Toxicity of Regimen(36 Months)
- Overall Response Rate(Every 6 weeks)
- Overall Survival (OS) According to Baseline Serum Hsp27 Level.(36 months)
- Hsp27 Expression in Archival Tissue(Cycle 1)
- Effect of Therapy Regimen on Circulating Tumor Cells (CTCs)and Correlative Analysis of Telomerase Activity(Prior to screening, prior to first loading dose, and prior to cycles 1, 2, 3 and 5)
研究者
Noah Hahn, M.D.
Sponsor-Investigator
Hoosier Cancer Research Network