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Advanced Urothelial CarcinomaPhase 1/2NCT05687721

Copanlisib and Avelumab as a Maintenance Therapy for Advanced Bladder Cancer

A Phase 1/2 study testing copanlisib and Avelumab in people with Advanced Urothelial Carcinoma, run by VA Office of Research and Development at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Urothelial Carcinoma
What is being tested?
copanlisib and Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
2 Jun 2025to 2 Jun 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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:
  • a.Provision of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from the most recent primary or metastatic tumor biopsy or resection obtained prior to treatment with first line chemotherapy but within one year of enrollment, with no intervening systemic anti-cancer therapy. If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable. If a suitable tissue sample is not otherwise available, then a tissue from a de novo biopsy (core needle or excisional) should have been obtained prior to initiation of this study. However, this biopsy is not required for participation in this trial if he/she meets all other inclusion and exclusion criteria. When patients undergo biopsy, in addition to FFPE preparation, fresh tissue should be sent to VABHS for single-cell RNAseq and T cell receptor sequencing as specified in the addendum.
  • 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).
  • Controlled arterial hypertension (per investigator assessment

Who cannot join

  • Patients whose disease progressed by RECIST v1.1 on or after first-line platinum-based chemotherapy for urothelial cancer.
  • Patients who have had a major surgery within 4 weeks or major radiation therapy within 2 weeks prior to randomization. Prior palliative radiotherapy is permitted, provided it has been completed at least 48 hours prior to entering the study.
  • Patients who are receiving any other investigational agent within the preceding 4 weeks. Observational studies are permitted.
  • Prior treatment with a Phosphoinositide 3-kinase inhibitor.
  • Prior therapy with anti-PD1/PD-L1 monoclonal antibody for aBC. However, prior treatment with adjuvant nivolumab is allowed if it was discontinued over 12 months prior to the start of this trial.
  • Patients with known symptomatic central nervous system (CNS) metastases requiring steroids. These patients have poor prognosis and often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events. Patients with previously diagnosed CNS metastases are eligible if the participants have completed the treatment and have recovered from the acute effects of radiation therapy or surgery prior to treatment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable.
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  • Diagnosis of any other malignancy in past 3 years, except for adequately treated basal cell or squamous cell skin cancer, other Stage 0 or Stage 1 cancers, or incidental finding of prostate cancer during cystoprostatectomy.
  • Patients with symptomatic metastatic cancer, such as moderate to severe pain, impaired organ function or spinal cord compression.
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade > 3), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of asthma system controlled per the Global Initiative for Asthma 2015)
  • History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
  • HbA1c > 8.5% at Screening
  • Known prior or suspected hypersensitivity to study drugs or any component in the formulations.
  • Current or prior use of immunosuppressive medication within 7 days prior, except the following:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection)
  • Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
  • Patient with a history or concurrent condition of Interstitial Lung Disease.
  • Patients with an active bleeding diathesis.
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident (<6 months prior to enrollment), myocardial infraction (<6 months prior to enrollment), unstable angina, congestive heart failure (> New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  • Active infection requiring systemic therapy.
  • Positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) due to potential pharmacokinetic interactions with copanlisib.
  • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
  • Other severe acute or chronic medical conditions including, but not limited to pneumonitis; psychiatric condition including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Vaccination within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccine and COVID-19 vaccines).
  • Pregnant female patients, breastfeeding female patients, female patients of childbearing potential and male patients who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 60 days after the last dose of investigational product
  • History of noncompliance to medical regimens.
  • Patients unwilling to or unable to comply with the protocol.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Boston, Massachusetts, 02130-4817

Other trials in United States

About this study

Official title: A Phase II Trial With Copanlisib Plus Avelumab as a Maintenance Therapy for Metastatic Bladder Cancer After Platinum-based Chemotherapy

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.

Read the detailed description

Patients with advanced urothelial cancer will be treated with platinum-based chemotherapy. After chemotherapy, an imaging study will be performed to determine cancer response. If there is no disease progression, patients will be eligible for this study. After informed consent is obtained, patients are enrolled. The treatment include immunotherapy avelumab as the standard of care plus a study medication copanlisib. Both medications are administrated through intravenous infusion. Avelumab wil be given once every two weeks while copanlisib will be administrated on Day 1, 8 and 15 of every 4-week cycle. Patient will be followed up for disease progression.

Being tested
copanlisib, Avelumab
Keywords
Urinary Bladder Neoplasms, Phosphatidylinositol 3-Kinase, immunotherapy, copanlisib, pembrolizumab, Ureteral Neoplasms
Medical subject headings
Urinary Bladder Neoplasms, Ureteral Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • copanlisibDrug

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

  • AvelumabDrug

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

Study groups in NCT05687721
Study groupRoleWhat they receive
Therapeutic armExperimentalCopanlisib 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
Receives: Drug: copanlisib; Drug: Avelumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months into the trial

Secondary outcomes (4)

  1. Overall Survival

    Overall survival is defined as the length of time from the start of this trial treatment to the time of death from any cause

    Measured: 24 months

  2. Objective response rate

    Objective response rate is defined as the percentage of patients who have a partial or complete response at any time during this treatment of this trial

    Measured: 2 months

  3. Disease-control rate

    Disease-control rate is defined as the percentage of patients who have a partial or complete response or stable disease at any time during this treatment of this trial

    Measured: 2-8 months

  4. Adverse events

    Adverse events are defined as any untoward medical occurrence of subjects which does not necessarily have a causal relationship with the treatment

    Measured: up to 2 years into the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2023
  2. Study start2 Jun 2025
  3. Primary completion2 Jun 2025
  4. Study completion2 Jun 2025

Why it stopped: The study drug is not available.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single-arm study
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05687721
Sponsor's protocol ID
ONCA-016-21F
Other IDs
CX002545
Status last verified
Jun 2025
First submitted
6 Jan 2023
Last updated
15 Jun 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing copanlisib and Avelumab in people with Advanced Urothelial Carcinoma, run by VA Office of Research and Development at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 30 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: 6 months into the trial). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05687721.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2025.

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