Copanlisib and Avelumab as a Maintenance Therapy for Advanced Bladder Cancer

NCT05687721 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: ONCA-016-21FCX002545
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with metastatic bladder cancer are usually treated with chemotherapy. If their cancers do not progress after chemotherapy, they can be enrolled into this study and receive a standard-of-care immunotherapy medication named avelumab plus a study drug named copanlisib.

Conditions

Advanced Urothelial Carcinoma

Keywords

Urinary Bladder Neoplasms; Phosphatidylinositol 3-Kinase; immunotherapy; copanlisib; pembrolizumab; Ureteral Neoplasms

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The primary endpoint is PFS. PFS is defined as the time between initiation of the avelumab/copanlisib combination and tumor progression or death from any cause, with censoring of patients who are lost to follow-up.

  6 months into the trial

Secondary Outcomes (4)

• Overall Survival

  24 months

• Objective response rate

  2 months

• Disease-control rate

  2-8 months

• Adverse events

  up to 2 years into the study

Other Outcomes (1)

• Molecular Correlative Studies

  up to 2 years into the study

Study Arms (1)

Therapeutic arm

EXPERIMENTAL

Copanlisib will be administered through intravenous infusion (IV) at 60 mg on Day 1, 8 and 15, and avelumab will be administered 800 mg IV on Day 1 and 15 of each 4-week treatment cycle for up to 26 cycles

Drug: copanlisib; Drug: Avelumab

Interventions

copanlisib DRUG

intravenous infusion (IV) at 60 mg on Day 1, 8 and 15 of each 4-week treatment cycle for up to 26 cycles

Therapeutic arm

Avelumab DRUG

800 mg intravenous infusion on Day 1 and 15 of each 4-week treatment cycle for up to 26 cycles

Therapeutic arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female
• Age \> 18 years
• Diagnosis:
• Histologically or cytologically confirmed metastatic or recurrent urothelial carcinoma. OR
• Documented stage IV disease (T4b, Any N, M0; any T, Any N, M1a-b), or Stage IIIB (T1-T4a, N2-N3, M0), or subset of stage IIIA (T1-T4a, N1, M0)
• Completed prior first-line platinum-based chemotherapy at least 4 weeks and not more than 10 weeks after the last dose of first line chemotherapy.
• Patients without progressive disease as per RECIST v1.1 guideline (i.e., with an ongoing CR, PR, or SD) following completion of the first-line chemotherapy.
• Patient must be appropriate to receive Avelumab maintenance therapy
• Measurable disease after chemotherapy is not required:
• Patients must have had X-rays, CT/ MRI scans, PET or physical examinations completed within 28 days prior to initial administration of study medications.
• Patients may have no evidence of disease after platinum-based chemotherapy. These patients will be included in the study for all other analyses except ORR and irORR.
• Soft tissue disease that has been radiated within two months prior to registration is not assessable as measurable disease. Soft tissue disease that has been radiated two or more months prior to registration is assessable as measurable disease provided that the lesion has progressed following radiation. As the biology of previously irradiated tumors may be different from non-irradiated tumors, patients must have at least one measurable lesion outside the previously irradiated region in order to be considered to have measurable disease.
• Tumor samples:

You may not qualify if:

• Estimated life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) status 2 OR Karnofsky Performance Status scale 60%. For the safety lead-in phase, only patients with PS 0-1 will be included.
• Adequate bone marrow function, including:
• Leukocytes \> 3000/mm3
• Absolute neutrophil count (ANC) \> 1,500/mm3
• Platelets \> 100,000/mm3
• Hemoglobin \> 9 g/dL (may have been transfused).
• Adequate renal function, defined as estimated creatinine clearance 20 mL/minute as calculated using the Cockcroft-Gault equation. It has been shown that creatinine clearance 15 ml/minute did not significantly affect the pharmacokinetics of copanlisib.
• Adequate liver function, including:
• b.Total serum bilirubin 1.5 x upper limit of normal (ULN) c.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 2.5 x ULN d.Total serum bilirubin \< 3 x ULN for patients with Gilbert's syndrome or for patients with cholestasis due to compressive adenopathy of the hepatic hilum
• Serum pregnancy test (for females of childbearing potential) negative at screening.
• Male patients able to father children and female patients of childbearing potential and at risk for pregnancy must agree to use 2 highly effective methods of contraception throughout the study and for at least 60 days after the last dose of assigned treatment.
• Evidence of a signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
• Patients who are willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
• Controlled diabetes A1c \< 8.5%. For patients with newly diagnosed diabetes mellitus that cannot meet protocol requirements, a single rescreening (which includes all screening procedures) should be performed when the patient's diabetes is controlled and can meet protocol requirement for HbA1c).

Sponsors & Collaborators

• VA Office of Research and Development: lead
• Bayer: collaborator

Study Sites (1)

VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

Boston, Massachusetts, 02130-4817, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Ureteral Neoplasms

Interventions

copanlisib; avelumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases

Study Officials

• Chong-Xian Pan, MD PhD

  VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a single-arm study

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: January 18, 2023
• Study Start: June 2, 2025
• Primary Completion: June 2, 2025
• Study Completion: June 2, 2025
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)