Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Lung Neoplasms

Carcinoma

Carcinoma, Neuroendocrine

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Etoposide

Carboplatin

Immune Checkpoint Inhibitors

Immunomodulating Agents

Atezolizumab

Etoposide phosphate

Iron-Dextran Complex

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Carboplatin 5 AUC D1 plus Etoposide 100mg/m2 D1-D3 plus Atezolizumab 1200 mg, Q21, 4 Cycles and then maintenance Atezolizumab 1200 mg Q21

Carboplatin 5 AUC D1 plus Etoposide 100mg/m2 D1-D3, 4 Cycles and then observation

TECENTRIQ C/S.SOL.IN 1200MG/VIAL (20ML) 1 VIAL x 20ML

ETOPOSIDE/PHARMACHEMIE SOL.INF 100MG/5ML VIAL BT x 10 VIALS x 5 ML

Konstantinos N Syrigos

Georgios Evangelou

Large Cell Neuroendocrine Carcinoma (LCNEC) is a rare and aggressive form of cancer that presents significant challenges regarding treatment options and prognosis. In this trial, the effectiveness of Atezolizumab in treating metastatic LCNEC was evaluated. Atezolizumab is an anti-PD-L1 antibody that has shown promising results in other types of cancer, such as small-cell lung Cancer and non-small-cell lung cancer. The trial aimed to assess the efficacy and safety of atezolizumab in combination with chemotherapy as a potential treatment option for treatment-naive patients with metastatic LCNEC The trial was conducted as an open-label, non-randomized study, comparing Atezolizumab plus platinum etoposide to platinum etoposide alone in patients with metastatic LCNEC.

This trial is a prospective clinical study to evaluate the effectiveness of a combination treatment regimen for patients with metastatic Large Cell Neuroendocrine Carcinoma (LCNEC) originating from the lung. The trial occurred between March 2018 and August 2022 at the 3rd Department of Medicine, Kapodistrian Medical School of Athens. The institutional review board of Sotiria Chest Diseases Hospital of Athens approved it. The trial adhered to Good Clinical Practice guidelines and the Declaration of Helsinki, and all patients or their legal representatives provided informed consent.

Patients:

The trial enrolled patients with metastatic LCNEC originating from the lung. Eligible patients had not received prior systemic treatment for LCNEC. Patients with brain metastases at diagnosis underwent Whole Brain Radiotherapy (WBRT) before starting systemic treatment.

Study Design:

The experimental group received a combination treatment regimen consisting of four cycles of Carboplatin, Etoposide, and Atezolizumab every 21 days.

Patients who achieved stable disease (SD) or a response (partial or complete) continued maintenance treatment with Atezolizumab until disease progression or discontinuation due to severe adverse events.

The control group received four cycles of Carboplatin and Etoposide. Immune checkpoint inhibitors were not allowed in later lines of treatment for the control group.

Response to therapy was assessed using CT scans and physical evaluations.

Endpoints:

Progression Free Survival (PFS): The time from treatment initiation to disease progression or death.

Overall Survival (OS): The time from treatment initiation to death. Overall Response Rate (ORR): The percentage of patients with a complete or partial response based on RECIST v1.1 criteria.

Duration of Response (DoR): The length of time the disease responded to treatment without progression on imaging studies.

Procedure:

Patients were treated at the 3rd Department of Medicine, Kapodistrian Medical School of Athens.

Approval for immunotherapy was obtained from the National Organisation for the Provision of Health Services (EOPYY) for each patient.

Blood samples for miR-375 and miR-21 analysis were collected at specific time points and processed according to standard procedures.

Analysis of miRNA expression was performed using the miRCURY LNA SYBR Green PCR Kit.

Statistical Analysis:

Rstudio was used for statistical analysis. The trial did not include a power analysis. The intention-to-treat principle was followed. Kaplan-Meier methods and Cox Regression survival analysis were used to estimate PFS and OS.

An analysis of the significance of the difference in characteristics between the experimental and control groups was conducted.

miR-21 and miR-375 Analysis:

Control samples for miR-21 and miR-375 were collected from volunteers without a cancer diagnosis, matching age with LCNEC patients.

Blood samples were collected at specific time points and processed to isolate plasma.

RNA was isolated from plasma samples, followed by cDNA synthesis and miRNA quantification using the miRCURY LNA SYBR Green PCR Kit.

MiR-103a-3p was used as a reference gene. Real-time PCR was performed to quantify miRNAs, and the results were expressed relative to the control group.

Atezolizumab in Large Cell Neuroendocrine Carcinoma

Effectiveness of Atezolizumab in Large Cell Neuroendocrine Carcinoma of the Lung and the Value of miR21 and miR-375 as Biomarkers

Progression Free Survival (PFS) was defined as the time from treatment initiation to disease progression οr death. Patients alive without progression at the last follow-up were censored at the date of the deadline for follow-up

Overall survival (OS) was defined as the time from treatment initiation to death, and patients alive during the last follow-up were censored at the date of the deadline for follow-up

Oncology Center of Biochemical Education And Research

Symptoms and General Pathology

Recurrence

Small Cell Lung Carcinoma

Disease Attributes

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Nivolumab

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive nivolumab IV on day 1 of a 28 day cycle. Patients also receive temozolomide PO on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Dwight Owen, MD, MS

This phase II trial studies how well nivolumab and temozolomide work in treating patients with small-cell lung cancer that has come back or does not respond to treatment, or neuroendocrine cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab and temozolomide may work better in treating patients with small-cell lung cancer and neuroendocrine cancer.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy (using response rate per RECIST v1.1) of nivolumab and temozolomide for the treatment of patients with either small cell lung cancer that have progressed or recurred after prior platinum-based chemotherapy and immunotherapy (cohort 1), or progressive metastatic neuroendocrine carcinoma of any grade or primary site in any line of therapy (cohort 2).

SECONDARY OBJECTIVES:

I. To evaluate the safety profile and toxicity of combination nivolumab and temozolomide as per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.

II. To evaluate the progression free survival (PFS) and overall survival (OS) of patients treated with combination nivolumab and temozolomide.

III. To evaluate the central nervous system (CNS) PFS of patients with small cell lung cancer (SCLC) treated with nivolumab and temozolomide.

EXPLORATORY OBJECTIVES:

I. To determine whether treatment with nivolumab and temozolomide leads to a decrease in immune-suppressive cell populations (ie myeloid-derived suppressor cells \[MDSC\]) in peripheral blood.

II. To determine whether objective response rate (ORR), PFS, OS vary by tumor O6-methylguanine deoxyribonucleic acid (DNA) methyltransferase (MGMT) methylation at baseline.

III. To determine whether baseline tumor mutational burden is predictive of response to therapy in patients with SCLC treated with nivolumab and temozolomide.

IV. To determine whether changes in blood based mutation burden during treatment may predict clinical benefit.

V. To determine whether a composite immune and tumor cell staining score can be developed with or without PD-L1 by immunohistochemistry (IHC) to predict response in the SCLC cohort.

OUTLINE:

Patients receive nivolumab intravenously (IV) on day 1 of a 28 day cycle. Patients also receive temozolomide orally (PO) on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 8 weeks for 12 months, then every 12 weeks thereafter.

Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer

A Phase II, Multi-Cohort Trial of Combination Nivolumab and Temozolomide in Recurrent/Refractory Small-Cell Lung Cancer and Advanced Neuroendocrine Tumors

The study will evaluate PD-L1 by immunohistochemistry (IHC), and assess the clinical outcomes (ie OS) between patients with high expression and low expression of PD-L1.

Response will be defined by a complete response (CR) or partial response (PR), confirmed or unconfirmed. Response will be defined for patients with measurable disease and who receive at least one dose of combination treatment. Exact binomial 95% confidence intervals for the true PR+CR response rate will be calculated.

Attribution to drug, time-of-onset, duration of the event, resolution, and any concomitant medications administered will be recorded. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either ?unrelated? or ?unlikely to be related? to study treatment in the event of an actual relationship developing.

CNS PFS will be measured for patients with relapsed vs refractory small-cell lung cancer (SCLC) in cohort 1. The Kaplan-Meier method will be used.

Bristol-Myers Squibb

Dwight Owen

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Death

Carcinoma, Small Cell

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Small Cell Carcinoma of the Bladder

Avelumab

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

National Cancer Institute (NCI)

Gland and Hormone Related Diseases

Carcinoma, Squamous Cell

Prostatic Neoplasms

Carcinoma, Renal Cell

Carcinoma, Ductal

Carcinoma, Transitional Cell

Adenocarcinoma, Clear Cell

Carcinoma, Medullary

Leydig Cell Tumor

Sertoli Cell Tumor

Urethral Neoplasms

Penile Neoplasms

Thyroid Neoplasms

Thyroid Diseases

Genital Neoplasms, Male

Genital Diseases

Genital Diseases, Male

Neoplasms, Squamous Cell

Kidney Neoplasms

Kidney Diseases

Urethral Diseases

Penile Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Endocrine System Diseases

Sertoli-Leydig Cell Tumor

Sex Cord-Gonadal Stromal Tumors

Testicular Neoplasms

Testicular Diseases

Gonadal Disorders

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Transitional Cell Carcinoma

Penile Cancer

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

Chromophobe Renal Cell Carcinoma

Thyroid Cancer, Medullary

Collecting Duct Carcinoma

Renal Medullary Carcinoma

Urethral Cancer

Urachal Adenocarcinoma

Sertoli-leydig Cell Tumors

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Patients receive cabozantinib PO, nivolumab IV and ipilimumab IV while on study. Patients undergo CT scan, MRI, PET and bone scans throughout the study.

Bone Scan

Cabozantinib S-malate

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Site Public Contact

Arnab Basu

Lance C. Pagliaro

Uzair B. Chaudhary

Anishka D'Souza

Nancy A. Dawson

Tareq Al Baghdadi

Hatem Hassanein

Mehmet A. Bilen

John M. Schallenkamp

Jeffrey A. Sosman

Thomas C. Westbrook

Walter M. Stadler

Vamsi K. Vasireddy

Bryan A. Faller

Ami Badami

Andrea B Apolo

This phase II trial studies how well cabozantinib works in combination with nivolumab and ipilimumab in treating patients with rare genitourinary (GU) tumors that that has spread from where it first started (primary site) to other places in the body. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib, nivolumab, and ipilimumab may work better in treating patients with genitourinary tumors that have no treatment options compared to giving cabozantinib, nivolumab, or ipilimumab alone.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of cabozantinib s-malate (cabozantinib) combined with nivolumab and ipilimumab in the first or second-line (and beyond) setting for patients within each of the rare genitourinary (GU) variant histology group of interest, as measured by objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

II. To estimate the overall survival (OS) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

III. To estimate the clinical benefit rate (defined as complete response \[CR\] or partial response \[PR\] or stable disease \[SD\]) for patients treated with cabozantinib combined with nivolumab and ipilimumab within each rare variant histology.

IV. To assess the safety of treating patients with rare variant histologies with cabozantinib combined with nivolumab and ipilimumab.

V. To support tissue banking and collection of clinical follow-up data for GU tract rare histological variants.

EXPLORATORY OBJECTIVES:

I. To assess effects of treatment in patients with bone-only disease by bone scan.

OUTLINE:

Patients receive cabozantinib orally (PO), nivolumab intravenously (IV) and ipilimumab IV while on study. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) and bone scans throughout the study.

Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors

A Phase II Study of Ipilimumab, Cabozantinib, and Nivolumab in Rare Genitourinary Cancers (ICONIC)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

The bone-only tumor patients will be evaluated in an exploratory fashion (if no RECIST measurements are available). A maximum of 15 patients with bone-only disease will be enrolled and evaluated using PFS for a descriptive analysis of the effect of treatment.

An objective response is defined as a confirmed complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Will be estimated by the number of confirmed objective responses divided by the total number of evaluable patients. Confidence intervals for the true ORR will be calculated.

Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a CR or PR to the earliest date progression is documented.

The median its 95% confidence interval will be determined and will be summarized using the Kaplan-Meier estimator.

A confirmed clinical benefit is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart or a confirmed stable disease at two consecutive tumor assessments at least 3 months apart. The CBR will be estimated by the number of patients with confirmed clinical benefit divided by the total number of evaluable patients. Confidence intervals for the true CBR will be calculated using exact binomial confidence intervals.

Will be assessed using Common Terminology Criteria for Adverse Events version 5.0. The maximum of a particular AE will be determined for each patient. Tables will summarize the number and relative frequency of patients observing an AE as well as the number and relative frequency of patients experiencing any AE of grade 3 or greater.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Atezolizumab in Large Cell Neuroendocrine Carcinoma	NCT06049966	Large Cell Neur...	Atezolizumab Carboplatin Etoposide	18 Years - 90 Years	Oncology Center of Biochemical Education And Research
Nivolumab and Temozolomide in Treating Patients With Recurrent or Refractory Small-Cell Lung Cancer or Advanced Neuroendocrine Cancer	NCT03728361	Grade I Neuroen... Grade II Neuroe... Grade III Neuro... Metastatic Neur... Neuroendocrine ... Recurrent Small... Refractory Smal... Lung Cancer Sta... Large Cell Neur... Neuroendocrine ... Small Cell Lung... Small-cell Lung...	Nivolumab Temozolomide	18 Years -	Ohio State University Comprehensive Cancer Center
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)
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors	NCT03866382	Bladder Adenoca... Bladder Clear C... Bladder Mixed A... Bladder Neuroen... Bladder Small C... Bladder Squamou... Chromophobe Ren... Collecting Duct... Invasive Bladde... Invasive Bladde... Invasive Bladde... Invasive Bladde... Invasive Bladde... Invasive Bladde... Kidney Medullar... Large Cell Neur... Malignant Testi... Malignant Testi... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Blad... Metastatic Chro... Metastatic Kidn... Metastatic Mali... Metastatic Papi... Metastatic Peni... Metastatic Pros... Metastatic Sarc... Metastatic Uret... Papillary Renal... Sarcomatoid Ren... Stage IV Bladde... Stage IV Penile... Stage IV Renal ... Stage IV Urethr... Stage IVB Prost... Urachal Adenoca... Urethral Clear ...	Bone Scan Cabozantinib S-... Computed Tomogr... Ipilimumab Magnetic Resona... Nivolumab Positron Emissi...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for large cell neuroendocrine carcinoma