CHARIOT: a Phase 1b/2 Study of Androgen Deprivation Therapy and Copanlisib in High-Risk Localized Prostate Cancer Patients Prior to Radical Prostatectomy
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 37
- 主要终点
- Phase 2 determine the rate of pCR or MRD at Radical Prostatectomy
研究概览
简要总结
The researchers are doing this study to find out whether copanlisib in combination with degarelix, given before standard surgical treatment (radical prostatectomy), is a safe and effective treatment that causes few or mild side effects for people who have localized high-risk prostate cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Willing and able to provide written informed consent and privacy authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
- •Individuals with prostate cancer 18 years of age and above
- •Histological or cytological evidence of prostate cancer
- •Documented high-risk localized prostate cancer based on one or more of the following NCCN criteria:
- •PSA >20ng/ml or
- •Gleason ≥8 or
- •Clinical stage ≥cT3a
- •Known PTEN status:
- •PTEN loss by IHC for participants in the PTEN loss cohort
- •PTEN intact by IHC for participants in the exploratory PTEN intact cohort (only available if PTEN intact cohort is opened)
- •Candidate for RP as determined by treating physician
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Appendix A: Performance Status Criteria)
- •Normal organ function with acceptable initial laboratory values within 28 days of registration:
- •ANC ≥ 1.5 K/mcL
- •Hemoglobin ≥ 9g/dL
- •Platelet count ≤100 K/mcL
- •Creatinine ≤ 1.5 x the institutional upper limit of normal (ULN)
- •Potassium within institutional normal range
- •Total Bilirubin ≤ 1.5 x ULN (Note: In participants with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, participant may be eligible)
- •SGOT (AST) ≤ 2.5 x ULN
- •SGPT (ALT) ≤ 2.5 x ULN
- •GFR (MDRD) ≥ 30 mL/min/1.73 m^2
- •Participants must agree to use a medically acceptable method of birth control (i.e., spermicide in conjunction with a barrier such as a condom) or sexual abstinence prior to registration, for the duration of study participation and for at least 5 months after the last treatment with copanlisib.
排除标准
- •Radiographic evidence of distant (extra-pelvic) metastatic prostate cancer on CT and/or MRI, bone scan or PET scan
- •On ADT (GnRH agonists or antagonists) for > 4 weeks at time of consent
- •Prior radiation to prostate
- •Medical conditions such as uncontrolled hypertension or cardiac disease that would, in the opinion of the investigator preclude participation in this protocol
- •A diagnosis of diabetes (type 1 or 2) on medications for the purpose of treating hyperglycemia or HgbA1C > 7 will be excluded from study
- •Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for basal or squamous cell skin cancer or superficial bladder cancer that has previously been treated.
- •Use of any prohibited concomitant medications including herbal supplements Medications With the Potential for Drug-Drug Interactions) within 2 weeks prior to treatment start
- •Receiving any other investigational agents within 4 weeks or 5x the half-life of investigational agent (whichever is longer) from this study's treatment start
- •Known allergy to any of the compounds under investigation
- •Any other condition which, in the opinion of the Investigator, would preclude participation in this trial
研究组 & 干预措施
Copanlisib in Combination With Degarelix
Phase 1b: The starting Dose level 1 will be 45 mg with the intent of dose escalating to the standard dose of 60 mg approved for heme malignancy. In the event of > =2 DLT at Dose level 1 (45 mg) the study will be terminated. If >= 2 DLT in patients at Dose level 2 (60 mg), Dose level 1 (45 mg) will be the RP2D if <= 1 DLT out of 6 patients at this dose.
Phase 2: Patients may dose reduce at the discretion of the investigator to the lowest dose of 45 mg. Participants who do not tolerate the copanlisib dose of 45 mg must discontinue study treatment permanently.
干预措施: Copanlisib (Drug)
Copanlisib in Combination With Degarelix
Phase 1b: The starting Dose level 1 will be 45 mg with the intent of dose escalating to the standard dose of 60 mg approved for heme malignancy. In the event of > =2 DLT at Dose level 1 (45 mg) the study will be terminated. If >= 2 DLT in patients at Dose level 2 (60 mg), Dose level 1 (45 mg) will be the RP2D if <= 1 DLT out of 6 patients at this dose.
Phase 2: Patients may dose reduce at the discretion of the investigator to the lowest dose of 45 mg. Participants who do not tolerate the copanlisib dose of 45 mg must discontinue study treatment permanently.
干预措施: Degarelix (Drug)
Copanlisib in Combination With Degarelix
Phase 1b: The starting Dose level 1 will be 45 mg with the intent of dose escalating to the standard dose of 60 mg approved for heme malignancy. In the event of > =2 DLT at Dose level 1 (45 mg) the study will be terminated. If >= 2 DLT in patients at Dose level 2 (60 mg), Dose level 1 (45 mg) will be the RP2D if <= 1 DLT out of 6 patients at this dose.
Phase 2: Patients may dose reduce at the discretion of the investigator to the lowest dose of 45 mg. Participants who do not tolerate the copanlisib dose of 45 mg must discontinue study treatment permanently.
干预措施: Radical Prostatectomy (Procedure)
结局指标
主要结局
Phase 2 determine the rate of pCR or MRD at Radical Prostatectomy
时间窗: 2 years
pCR will be defined as the absence of morphologically identifiable carcinoma in the RP specimen. MRD will be defined as ≤ 5mm of residual tumor in the RP specimen.
phase Ib determine the recommended phase 2 dose (RP2D) of copanlisib in combination with degarelix
时间窗: 1 year
DLTs are any of the following events not clearly due to the underlying disease or extraneous causes. Toxicities will be evaluated using CTCAE version 5.0 (CTCAE v5.0). Only toxicities that meet DLT definitions within the DLT assessment window (one 28-day cycle) and are attributed to degarelix, copanlisib or copanlisib plus degarelix will be counted as DLTs.
次要结局
未报告次要终点