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Small Cell Carcinoma of the BladderPhase 2NCT06228066

Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)

A Phase 2 study testing Lurbinectedin and Avelumab in people with Small Cell Carcinoma of the Bladder and High Grade Neuroendocrine Tumors of the Urinary Tract, run by National Cancer Institute (NCI) at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Background: Small cell carcinoma of the bladder (SCCB) and other high-grade neuroendocrine tumors (HGNET) of the urinary tract are rare but aggressive cancers. Average survival for people diagnosed with SCCB or HGNET is about 1 year. Lurbinectedin and avelumab are drugs that are approved to treat other cancers. Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
Lurbinectedin and Avelumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
13 Jun 2024to 1 Sep 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed metastatic small cell carcinoma of the bladder (SCCB) or other high grade neuroendocrine tumors (HGNETs) of the urinary tract (which includes renal pelvis, ureter, and urethra, and excludes neuroendocrine tumors of the prostate). Mixed histologies, with any component including SCCB or HGNETs, are eligible for inclusion.
  • Prior treatment as follows:
  • For Cohort 1: Participants must have received prior ICIs (PD-1 or PD-L1) or be ineligible for treatment with ICIs.
  • For Cohort 2: Participants must be ICI naive but eligible to receive them.
  • Participants must have metastatic disease defined as new or progressive lesions.
  • Participants must have at least one measurable site of disease, per RECIST 1.1.
Show all 32Show fewer
  • Participants must have received, be ineligible, or refused prior platinum/etoposide chemotherapy for SCCB or other HGNET of the urinary tract. Platinum ineligibility is defined as a CrCl <30, or two or more of the following: CrCl <50-60, ECOG >=2, hearing loss >= grade 2, peripheral neuropathy >= grade 2, New York Heart Association (NYHA) heart failure class >= class III.
  • Age >=18 years.
  • Eastern Cooperative Oncology Group [ECOG] performance status (PS) <=2 (Karnofsky >=60%).
  • Adequate organ and marrow function as defined below:
  • Absolute neutrophil count (ANC) >=1,500/microliter
  • Platelets >=100,000/ microliter
  • Hemoglobin (Hgb) > 9g/dL (erythrocyte transfusions are allowed to achieve acceptable Hgb)
  • Total bilirubin within normal limits with the following exceptions:
  • Participants with tumor involving the liver may have mild to moderate hepatic impairment with total bilirubin <= 1.5 x upper limit of normal (ULN)
  • Participants with known Gilbert disease who have serum bilirubin level <= 1.5 x ULN
  • Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) <=1.5 x institutional ULN
  • ---Participants with tumor involving the liver with AST and ALT <= 5.0 x ULN and bilirubin <= 1.5 x ULN may be eligible.
  • Creatinine clearance (CrCl) >= 30 mL/min/1.73 m^2 (glomerular filtration rate [GFR] may be used in place of CrCl. Creatinine clearance or eGFR should be calculated per institutional standard)
  • Creatine phosphokinase (CPK) <= 2.5 x ULN
  • Participants with previously treated brain metastases or central nervous system (CNS) metastases are eligible if they have recovered from any acute effects of radiotherapy and not requiring steroids, and any whole brain radiation therapy or any stereotactic radiosurgery was completed at least 2 weeks prior to initiation of therapy.
  • Human immunodeficiency virus (HIV) positive participants are eligible if on stable dose of highly active antiretroviral therapy (HAART), CD4 counts are > 350 cells/mm^3 and viral load is undetectable.
  • Hepatitis B virus (HBV) positive participants are eligible if they have been treated or are on an appropriate course of antivirals at study entry and with planned monitoring and management according to appropriate guidance including prophylaxis.
  • Hepatitis C virus (HCV) positive participants are eligible if:
  • they are on active HCV therapy at study entry or are on an appropriate course of antivirals without documented clinically significant impaired liver function test or hematologic abnormalities and with planned monitoring and management according to appropriate labeling, or if they are post-treatment for HCV; or
  • they have a negative polymerase chain reaction (PCR).
  • Systemic corticosteroid therapy (defined as >= the equivalent of prednisone 10 mg/day) or other immunosuppressive agents such as azathioprine or cyclosporin must be discontinued at least 1 week prior to treatment initiation for recent short course use (<=14 days) or discontinued at least 4 weeks prior to treatment initiation for long term use (>14 days).
  • Contraception requirements as follows:
  • Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (e.g., intrauterine device [IUD], hormonal, surgical sterilization, abstinence) prior to study entry, for the duration of study participation, and for up to six (6) months after discontinuation of the study drug(s).
  • Individuals able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to six (6) months after the last dose of the study drug(s). We also will recommend individuals able to father a child with IOCBP partners to ask the partners to be on an effective birth control (hormonal, intrauterine device (IUD), surgical sterilization). Individuals able to father a child must not freeze or donate sperm within the same period.
  • Nursing participants must be willing to discontinue nursing from study treatment initiation through six (6) weeks after the last dose of the study drug(s).
  • Participants must be able to understand and willing to sign a written informed consent document.

Who cannot join

  • Prior investigational drug, chemotherapy, immunotherapy or any prior radiotherapy (except for palliative bone directed therapy) within the past 14 days prior to the first drug administration. Additionally, FDA-approved hormonal therapy for the treatment or prevention of other malignancies (e.g., breast cancer, prostate cancer) may be continued where in the opinion of the investigator stopping such therapies may increase the risk of disease progression. Potential drug-drug interactions with the hormonal agent will be assessed by the enrolling investigator prior to enrollment.
  • Participants previously treated with lurbinectedin.
  • History of anaphylactic allergic reactions attributed to compounds of similar chemical or biologic composition to lurbinectedin or avelumab
  • Symptomatic or untreated CNS metastases
  • For Cohort 2: Active autoimmune disease that might deteriorate when receiving avelumab with the exception of:
  • Diabetes type I, eczema, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment
Show all 13Show fewer
  • Requirement of hormone replacement with corticosteroids if the steroids are administered only for the purpose of hormonal replacement and at doses <= 10mg of prednisone or equivalent per day
  • Requirement of steroids for other conditions through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation)
  • Physiologic doses of corticosteroids (<= the equivalent of prednisone 10 mg/day). The use of corticosteroids as premedication for contrast-enhanced studies is allowed prior to treatment initiation and on study.
  • Prior organ transplantation including allogenic stem cell transplantation.
  • Participants who have received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus and locally authorized/approved COVID-19 vaccines are permitted.
  • Pregnant people as evaluated by a positive serum or urine beta-human chorionic gonadotropin (beta-hCG) test
  • Severe uncontrolled intercurrent illness that would limit compliance with study requirements, evaluated by history, physical exam, and chemistry panel.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

NCIMO Referral Office contact

(888) 624-1937

ncimo_referrals@mail.nih.gov

Andrea B Apolo, M.D. contact

(301) 480-0536

apoloab@mail.nih.gov

United States1 site, 1 recruiting

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

    Lisa Ley, 240-858-3524, lisa.ley@nih.gov

    National Cancer Institute Referral Office, (888) 624-1937

    Recruiting

Other trials in United States

About this study

Official title: A Phase II Study of Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)

Background:

Small cell carcinoma of the bladder (SCCB) and other high-grade neuroendocrine tumors (HGNET) of the urinary tract are rare but aggressive cancers. Average survival for people diagnosed with SCCB or HGNET is about 1 year. Lurbinectedin and avelumab are drugs that are approved to treat other cancers. Researchers want to see if these drugs can help people with SCCB or HGNET.

Read more

Objective:

To test lurbinectedin with or without avelumab in people with SCCB or HGNET.

Eligibility:

Adults aged 18 years and older with SCBB or HGNET that returned and spread after treatment.

Design:

Participants will be screened. They will have a physical exam. They will have blood tests and imaging scans. They may need to have a new biopsy: A small needle will be used to collect a tissue sample from the tumor.

Both study drugs are given through a tube attached to a needle inserted into a vein. If participants have already received a drug like avelumab they will receive only lurbinectedin. If patients have not been previously treated with a drug like avelumab they will receive both lurbinectedin and avelumab. All participants will receive their treatment once every 3 weeks for up to 10 years. They will also receive other drugs to relieve adverse effects.

Biopsies, blood tests, and imaging scans will be repeated during some study visits. Participants may also have urine tests and tests of their heart function.

Participants may remain in the study as long as the treatment is helping them. If they stop treatment, they will have safety visits 14, 30, and 90 days after their last dose. Additional follow-up visits will continue 5 to 10 years.

Read the detailed description

Background:

  • Small cell carcinoma of the bladder (SCCB) is a rare, aggressive form of bladder cancer, accounting for less than 1% of all bladder malignancies.
  • High grade neuroendocrine tumors (HGNET) of the urinary tract are very rare and include both small cell neuroendocrine carcinomas (SCNEC) and large cell neuroendocrine carcinomas (LCNEC).
  • Traditionally regimens drawn from the small cell lung cancer literature (cisplatin and etoposide) are used in the frontline setting, and while initially highly responsive to chemotherapy, responses are generally short lived.
  • There is little evidence to guide therapeutic decisions at time of disease progression.
  • Lurbinectedin is a selective inhibitor of oncogenic transcription that binds preferentially to guanines located in the GC-rich regulatory areas of DNA gene promoters.
  • Lurbinectedin prevents binding of transcription factors to their recognition sequences, inhibiting oncogenic transcription and leading to tumor cell apoptosis.
  • Lurbinectedin was recently approved as a second line agent in small cell lung cancer, where it has shown an overall response rate of 35%.
  • Immune checkpoint inhibitors (ICIs) have become part of the standard of care for small cell lung cancer, and their use in the community for treatment of SCCB has increased.
  • However, ICI use in SCCB is still case reportable in the literature, and no prospective studies have been published to date.

Objective:

-To assess the objective response rate (ORR) of lurbinectedin, either alone or in combination with avelumab, in participants with small cell carcinoma of the bladder (SCCB) or other high grade neuroendocrine tumors (HGNETs) of the urinary tract

Eligibility:

  • Age >= 18 years
  • Histologically confirmed diagnosis of metastatic SCCB or HGNET of the urinary tract
  • Participants must have metastatic disease defined as new or progressive lesions.
  • Participants must have at least one measurable site of disease
  • Participants must have received, be ineligible, or refused prior platinum/etoposide chemotherapy for SCCB or HGNET of the urinary tract.

Design:

  • This is a Phase II, multisite, open label, nonrandomized study with two cohorts.
  • All participants will receive lurbinectedin.
  • Participants without prior ICI exposure will be eligible to receive concurrent avelumab.
  • Treatment will be given in 21-day cycles continuously for up to 10 years or until signs of progression or intolerable side effects.
  • Lurbinectedin will be administered intravenously (I.V.) at 3.2mg/m^2 every 21 days.
  • Avelumab will be administered I.V. at 800mg every 21 days.
  • The accrual ceiling will be set at 35 to allow for a small number of inevaluable participants.
Being tested
Lurbinectedin, Avelumab
Keywords
High grade neuroendocrine tumors, small cell neuroendocrine carcinoma, large cell neuroendocrine carcinoma, transcription factor inhibitor, Immunotherapy, programmed cell death 1 ligand 1
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

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

  • LurbinectedinDrug

    Lurbinectedin is administered IV over 1 hour at 3.2 mg/m^2 on day 1 of each 21-day cycle

  • AvelumabDrug

    Avelumab is administered IV at 800 mg over 1 hour on day 1 of each 21-day cycle

Study groups in NCT06228066
Study groupRoleWhat they receive
Arm 1ExperimentalTreatment with lurbinectedin
Receives: Drug: Lurbinectedin
Arm 2ExperimentalTreatment with lurbinectedin and avelumab
Receives: Drug: Lurbinectedin; Drug: Avelumab

What is being measured

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

  1. Objective response rate (ORR)

    Percentage of participants by best overall response (e.g., CR, PR, SD, PD) to therapy

    Measured: At every restaging (prior to every 3rd cycle) until the end of the treatment

Secondary outcomes (5)

  1. Safety of lurbinectedin with or without avelumab

    Adverse events (AEs) will be reported by type and grade of toxicity

    Measured: From first dose through 90 days after last treatment with the study drug(s)

  2. Clinical benefit rate (CBR)

    Percentage of participant who have achieved CR, PR, and SD while on treatment.

    Measured: At every restaging (every 9 weeks) until the end of the study therapy

  3. Progression-free survival (PFS)

    Duration of time from start of treatment to time of progression or death, whichever occurs first

    Measured: At every restaging (every 9 weeks) until PD

  4. Overall survival (OS)

    Time from the start of treatment that participants are still alive.

    Measured: Day 1 of each cycle, at EoT, at the Safety visits, and every 90 days for up to a total of 10 years after the end of therapy.

  5. Duration of response (DoR)

    Time from start of treatment to disease progression or death in participants who achieve CR or PR

    Measured: At each study visit and at every restaging (every 9 weeks) starting at cycle 3 until PD

Timeline

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

  1. First posted29 Jan 2024
  2. Study start13 Jun 2024
  3. Primary completion1 Sep 2027 (estimated)
  4. Study completion1 Sep 2028 (estimated)

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06228066
Sponsor's protocol ID
10001523
Other IDs
001523-C
Status last verified
13 Oct 2026
First submitted
26 Jan 2024
Last updated
16 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All collected IPD will be shared@@@@@@

Publications

  • Simon N, Chandran E, Atiq S, Kydd AR, Girardi D, Ley L, Cordes L, Wang TF, Boudjadi S, Stukes I, Smith E, Akbulut D, Niglio S, Patel R, Banday R, Redd B, Gurram S, Steinberg S, Apolo AB. A phase II study of lurbinectedin with or without avelumab in small cell carcinoma of the bladder (laser)-design and rationale. Future Oncol. 2025 Apr;21(10):1171-1177. doi: 10.1080/14796694.2025.2480534. Epub 2025 Mar 21.

    PubMed 40116623

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lurbinectedin and Avelumab in people with Small Cell Carcinoma of the Bladder and High Grade Neuroendocrine Tumors of the Urinary Tract, run by National Cancer Institute (NCI) 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 32 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 16 Oct 2026. 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

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

Contact NCIMO Referral Office ((888) 624-1937, ncimo_referrals@mail.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: At every restaging (prior to every 3rd cycle) until the end of the treatment). 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 NCT06228066, which also lists 1 linked publication.

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 16 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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