Symptoms and General Pathology

All Conditions

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Death

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Pembrolizumab 200 mg administered as intravenous (IV) infusion every 3 weeks up to 24 months or until progression or unacceptable toxicity develops.

200 mg, administered as intravenous (IV) infusion every 3 weeks up to 24 months or until progression or unacceptable toxicity develops.

Eve MAUBEC, Pr

Zahia Ben-Abdesselam, CP

The purpose of this study is to assess the efficacy and safety of pembrolizumab in patient with locally advanced or metastatic squamous cell carcinoma of the skin

Agents blocking the Programmed Cell Death 1(PD1)/Programmed Cell Death 1-Ligand 1 (PD-L1) pathway have demonstrated objective, durable tumor regressions in patients with advanced solid malignancies and efficacy has been linked to PD-L1 expression. PD-L1 expression by tumour cells is the strongest single predictor of response to anti-PD1 therapy (J Taube, R Anders et al, Clin Cancer Res 2014). Pembrolizumab (MK-3475) is a high-affinity humanized monoclonal anti-PD1 antibody. It leads to dual PD1-ligand blockade of PD-L1 and PD-L2 that may reactivate the immune surveillance and elicit anti-tumour response. It has antitumor activity in melanoma and NSCLC (phase III trials). Pembrolizumab might be of interest in unresectable squamous cell carcinomas of the skin (SCCS).

Approximately 20% to 30% of non-melanoma skin cancers are SCCS. Most patients with primary SCCS have an excellent prognosis, but SCCS can progress to advanced stages that are impossible to treat by surgical excision or radiotherapy. Few therapeutic options are available for these tumors. Conventional chemotherapy, such as cisplatin-based combinations, has some efficacy, but the toxic effects of these combinations often prohibit their use in elderly patients. Epidermal Growth Factor (EGFR) signaling antagonists have activity only in a subset of patients. New therapeutic options are needed for patients with advanced SCCS.

No trial evaluating pembrolizumab in human SCCS is ongoing. Investigators hypothesize that:

i) PD-L1 is expressed in SCCS as in HNSCC ii) pembrolizumab may be effective as a single agent in patients with unresectable SCCS iii) Efficacy of pembrolizumab is correlated to PD-L1 expression in SCCS.

Investigators therefore intend to determine the efficacy and safety of single agent pembrolizumab in all patients and in patients with PD-L1-positive unresectable SCCS naïve of chemotherapy and of EGFR inhibitors.

Study of Pembrolizumab as First Line Therapy in Patients With Unresectable Squamous Cell Carcinoma of the Skin

Phase II Study of Pembrolizumab (MK-3475) as First Line Single Drug Therapy in Patients With Unresectable Squamous Cell Carcinoma of the Skin

Response rate (RR) at 15 weeks (RECIST v.1.1) in the whole sample by CT or MRI Response Evaluation Criteria in Solid Tumors with central radiology review

Advers event and serious adverse event status

To assess in the whole sample and in PD-L1 positive patients

The best response was collected after all radiological evaluation completion

Assistance Publique - Hôpitaux de Paris

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Urinary Bladder Neoplasms

Neuroendocrine Tumors

Small Cell Lung Carcinoma

Urologic Neoplasms

Carcinoma, Neuroendocrine

Carcinoma, Small Cell

Lung Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neuroendocrine Tumor

Small Cell Lung Cancer

Small Cell Carcinoma of the Bladder

Neuroepithelioma

Avelumab

Immunomodulating Agents

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	Link
Study of Pembrolizumab as First Line Therapy in Patients With Unresectable Squamous Cell Carcinoma of the Skin	NCT02883556	Carcinoma, Squa...	Pembrolizumab	18 Years -	Assistance Publique - Hôpitaux de Paris
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)

Spots Global Cancer Trial Database for programmed cell death 1 ligand 1