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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Copanlisib; Drug: Degarelix; Procedure: Radical Prostatectomy

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Suffolk - Commack (Limited Protocol Activities)
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Dana Rathkopf, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Androgen Deprivation Therapy; Copanlisib; Radical Prostatectomy; Degarelix
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 23-331

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No