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

Prostate Cancer Clinical Trial

Official title:

CHARIOT: A Phase 1b/2 Study of Androgen Deprivation Therapy and Copanlisib in High-Risk Localized Prostate Cancer Patients Prior to Radical Prostatectomy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06218667
• Other study ID #: 23-331
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 11, 2024
• Est. completion date: January 2027

Study information

• Verified date: January 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Dana Rathkopf, MD
• Phone: 646-422-4379
• Email: rathkopd[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: January 2027
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Copanlisib
Dose level 1 (starting dose): 45 mg of copanlisib IV weekly x 3 weeks on/1 week off Dose level 2 (standard dose): 60 mg of copanlisib IV weekly x 3 weeks on/1 week off
• Degarelix
Degarelix (GnRH antagonist): 240 mg loading dose sub-cutaneous once on C1D1; 80 mg maintenance dose on C2D1 and C3D1.

Procedure:
• Radical Prostatectomy
Standard treatment

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	Memorial Sloan Kettering Cancer Suffolk - Commack (Limited Protocol Activities)	Commack	New York
United States	Memorial Sloan Kettering Westchester (Limited Protocol Activities)	Harrison	New York
United States	Memorial Sloan Kettering Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Nassau (Limited Protocol Activities)	Uniondale	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	phase Ib determine the recommended phase 2 dose (RP2D) of copanlisib in combination with degarelix	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.	1 year
Primary	Phase 2 determine the rate of pCR or MRD at Radical Prostatectomy	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.	2 years

External Links

•   Memorial Sloan Kettering Cancer Center