Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Prostatic Neoplasms

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Neuroendocrine

Carcinoma, Small Cell

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Small Cell Lung Cancer

Kennedy Disease

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antibodies

Androgens

Immunomodulating Agents

Immunoglobulins

Hormones

Hormone Antagonists

Participants will be given Apalutamide tablets combined with infusions of Cetrelimab in 28-day cycles, for up maximum of two years.

Apalutamide

480 mg given through intravenous infusion (IV) on day 1 of every 28-day treatment cycle and administered over a 60-minute infusion

Cetrelimab

Rahul Aggarwal, MD

Despite the low androgen receptor (AR) transcriptional activity of treatment-emergent small cell neuroendocrine prostate cancer, there is persistent AR expression observed in the majority of treatment-emergent small-cell neuroendocrine prostate cancer (t-SCNC) biopsies. This indicates that epigenetic dysregulation leads to reprogramming away from an AR-driven transcriptional program. Therefore, continuation of AR blockade in the form of apalutamide may provide additive benefit compared to immune checkpoint blockade alone. The investigators hypothesize that the combination of apalutamide plus cetrelimab will achieve a clinically significant composite response rate with sufficient durability of response in mCRPC patients with evidence of treatment-emergent small cell neuroendocrine prostate cancer

This is a phase 2, single arm, Simon's two-stage evaluation of the combination of apalutamide plus cetrelimab in patients with mCRPC and histologic and/or genomic evidence of treatment-emergent small cell neuroendocrine prostate cancer who have previously progressed on at least one prior androgen signaling inhibitor.

Participants may continue study treatment from the time of treatment initiation until confirmed radiographic progressive disease (PD) per PCWG3 and RECIST 1.1 criteria, unequivocal clinical progression, unacceptable toxicity, or patient withdrawal, whichever occurs first, for a maximum of 24 months.

PRIMARY OBJECTIVE:

I. To determine the composite response rate as defined by achieving one or more of the following at any time point during study treatment:

1. Decline from baseline in serum PSA of \>= 50% (PSA50), confirmed by repeat measurement \>= 4 weeks later and/or
2. Objective response by RECIST 1.1 criteria

SECONDARY OBJECTIVES:

I. To determine safety of the combination as determined by CTCAE version 5.0.

II. To determine the median radiographic progression-free survival by PCWG3 criteria.

III. To determine the PSA50 and decline from baseline in serum PSA of \>= 90% (PSA90) response proportion achieved.

IV. To determine the median PSA progression-free survival.

V. To determine the median overall survival.

VI. To determine the objective response rate and median duration of response by RECIST 1.1 criteria.

Patients will be followed up for safety evaluations 30 days and 100 days after treatment completion. Patients will be followed for overall survival every 90 days (+/- 30 days) from last dose of study treatment, until death, withdrawal of consent, or the end of the study, whichever occurs first.

Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer

A Phase 2 Study of Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer

The composite response rate is determined by a combination of a decline from baseline in serum PSA of \>= 50%, confirmed by repeat measurement ≥ 4 weeks later (PSA50) AND/OR a complete response (CR) or partial response (PR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria

Proportion of participants with an adverse event determined to be related to study treatment, and classified using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0)

PFS is defined as the time from initiation of study treatment until radiographic progression by PCWG3 criteria or death, whichever occurs first.

Defined as the proportion of participants with a demonstrated \>= 50% decline from baseline serum PSA confirmed by repeat measurement \>= 4 weeks after first time point.

Defined as the proportion of participants with a demonstrated \>= 90% decline from baseline serum PSA confirmed by repeat measurement \>= 4 weeks after first time point.

PSA progression-free survival is defined as the time from initiation of study treatment until PSA progression as determined by PCWG3 criteria or death, whichever occurs first.

Overall survival from date of initiation of study treatment until death from any cause.

From initiation of study treatment until maximal percent decline from baseline in sum of longest diameter (SLD) of target lesions by RECIST 1.1 criteria

The length of time from a confirmed response until progression or death, whichever comes first.

Janssen Scientific Affairs, LLC

Rahul Aggarwal

Principal Investigator

Symptoms and General Pathology

Urinary Bladder Neoplasms

Urologic Neoplasms

Death

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Small Cell Carcinoma of the Bladder

Antineoplastic Agents

Avelumab

Antineoplastic Agents, Immunological

Treatment with lurbinectedin and avelumab

Lurbinectedin is administered IV over 1 hour at 3.2 mg/m2 on day 1 of each 21-day cycle

Lurbinectedin

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

NCIMO Referral Office

Andrea B Apolo, M.D.

Lisa Ley

National Cancer Institute Referral Office

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.

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.

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 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, immune checkpoint inhibitor 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 immune checkpoint inhibitor 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.

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

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

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

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

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

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

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer	NCT04926181	Small Cell Neur... Prostate Cancer Small Cell Carc...	Apalutamide Cetrelimab	18 Years -	University of California, San Francisco
Lurbinectedin With or Without Avelumab in Small Cell Carcinoma of the Bladder (LASER)	NCT06228066	Small Cell Carc... High Grade Neur...	Lurbinectedin Avelumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Apalutamide Plus Cetrelimab in Patients With Treatment-Emergent Small Cell Neuroendocrine Prostate Cancer	NCT04926181	Small Cell Neur... Prostate Cancer Small Cell Carc...	Apalutamide Cetrelimab	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for small cell neuroendocrine carcinoma