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

NCT06218667 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: 23-331
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Prostate Cancer

Keywords

Androgen Deprivation Therapy; Copanlisib; Radical Prostatectomy; Degarelix

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Study Arms (1)

Copanlisib in Combination With Degarelix

EXPERIMENTAL

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.

Drug: Copanlisib; Drug: Degarelix; Procedure: Radical Prostatectomy

Interventions

Copanlisib DRUG

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

Copanlisib in Combination With Degarelix

Degarelix DRUG

Degarelix (GnRH antagonist): 240 mg loading dose sub-cutaneous once on C1D1; 80 mg maintenance dose on C2D1 and C3D1.

Copanlisib in Combination With Degarelix

Radical Prostatectomy PROCEDURE

Standard treatment

Copanlisib in Combination With Degarelix

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

copanlisib; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Dana Rathkopf, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: January 23, 2024
• Study Start: January 11, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share