CHARIOT: a Phase 1b/2 Study of Androgen Deprivation Therapy and Copanlisib in High-Risk Localized Prostate Cancer Patients Prior to Radical Prostatectomy
Overview
- Phase
- Phase 1
- Intervention
- Copanlisib
- Conditions
- Prostate Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 37
- Primary Endpoint
- Phase 2 determine the rate of pCR or MRD at Radical Prostatectomy
- Status
- Withdrawn
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: Copanlisib
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.
Intervention: Degarelix
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.
Intervention: Radical Prostatectomy
Outcomes
Primary Outcomes
Phase 2 determine the rate of pCR or MRD at Radical Prostatectomy
Time Frame: 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
Time Frame: 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.