A Study of Copanlisib in Combination with Degarelix in People with Prostate Cancer

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:

  1. PSA \>20ng/ml or
  2. Gleason ≥8 or
  3. Clinical stage ≥cT3a
* Known PTEN status:

  1. PTEN loss by IHC for participants in the PTEN loss cohort
  2. 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.

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