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Copanlisib in Combination with Degarelix in Treating High-Risk Localized Prostate Cancer prior to Radical Prostatectomy, The CHARIOT Trial
Trial Status: temporarily closed to accrual
This phase 1b/2 trial studies the side effects and best dose of copanlisib in combination with degarelix, and how well the combination works in treating patients with high-risk prostate cancer that has not spread to other parts of the body (localized) prior to surgery to remove the entire prostate (radical prostatectomy). Copanlisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Degarelix binds to gonadotropin-releasing hormone (GnRH) receptors in the pituitary gland. This causes the body to stop making testosterone, which prostate cancer needs to grow. Giving copanlisib and degarelix prior to radical prostatectomy may work better than degarelix alone prior to radical prostatectomy in treating high-risk localized 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 National Comprehensive Cancer Network (NCCN) criteria:
* Prostate-specific antigen (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
Absolute neutrophil count (ANC) ≥ 1.5 K/mcL (within 28 days of registration)
Hemoglobin ≥ 9g/dL (within 28 days of registration)
Platelet count ≥ 100 K/mcL (within 28 days of registration)
Creatinine ≤ 1.5 x the institutional upper limit of normal (ULN) (within 28 days of registration)
Potassium within institutional normal range (within 28 days of registration)
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) (within 28 days of registration)
Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]) ≤ 2.5 x ULN (within 28 days of registration)
Serum glutamic-pyruvic transaminase (SGPT) (alanine transaminase [ALT]) ≤ 2.5 x ULN (within 28 days of registration)
Glomerular filtration rate (GFR) (Modification of Diet in Renal Disease [MDRD]) ≥ 30 mL/min/1.73 m^2 (within 28 days of registration)
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 androgen deprivation therapy (ADT) (gonadotropin-releasing hormone agonist [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 hemoglobin A1C (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 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
Additional locations may be listed on ClinicalTrials.gov for NCT06218667.
I. To determine the recommended phase 2 dose (RP2D) of copanlisib in combination with degarelix in participants with high-risk localized prostate cancer that has PTEN loss. (Phase 1b)
II. To determine the rate of pathological complete response (pCR) or minimal residual disease (MRD) at radical prostatectomy (RP) following three cycles of copanlisib and degarelix with loss of PTEN on immunohistochemistry (IHC). (Phase 2)
SECONDARY OBJECTIVES:
I. To determine safety.
II. To determine time to biochemical recurrence.
III. To determine metastasis-free survival.
EXPLORATORY OBJECTIVES:
I. To determine pCR or MRD rate in the exploratory cohort of participants with PTEN intact tumors.
II. To evaluate the following correlatives in relation to treatment response:
IIa. Intratumoral target inhibition;
IIb. Tissue analysis and sequencing;
IIc. Prostate magnetic resonance imaging (MRI).
OUTLINE: This is a phase 1b dose-escalation study of copanlisib, followed by a phase 2 study.
Patients receive copanlisib intravenously (IV) over 1 hour on days 1, 8 and 15 of each cycle and degarelix subcutaneously (SC) on day 1 of each cycle. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo standard radical prostatectomy. Patients also undergo computed tomography (CT) and/or MRI, as well as bone scan and/or positron emission tomography (PET) scan during screening. Patients also undergo MRI of the prostate during screening and on study. In addition, patients may optionally undergo collection of blood samples during screening.
After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for 2 years.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center