Neoplasms

All Conditions

Infections

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Merkel Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Merkel Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Nivolumab

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive nivolumab IV over 30 minutes at week 0. Treatments repeat every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients also receive radiation therapy on Monday-Friday or 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes at week 0. Treatments repeat every 2 weeks for nivolumab and 6 weeks for ipilimumab for up to 1 year in the absence of disease progression or unacceptable toxicity.

Radiation Therapy

Claire Verschraegen, MD

This phase I trial studies the side effects and how well nivolumab works when given together with radiation therapy or ipilimumab as adjuvant therapy in treating patients with Merkel cell cancer. 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. Radiation therapy uses high energy x-rays, gamma rays, neutrons, protons or other sources to kill tumor cells and shrink tumors. Giving nivolumab with radiation therapy or ipilimumab after surgery may kill any remaining tumor cells.

PRIMARY OBJECTIVES:

I. To assess the tolerability of two different experimental immunotherapy regimens in the adjuvant setting in patients with Merkel cell carcinoma (MCC).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability profile of each of the treatment using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

II. To assess the efficacy of each of the treatment arms according to recurrence-free survival (RFS) at one and half years, defined as the time between the date of randomization and the date of first progression (local, regional or distant metastasis) or death (whatever the cause), whichever occurs first.

III. To assess the efficacy of each of the treatment arms according to overall survival (OS) at three years, defined from the time of randomization and the date of death, compared to historical registry control.

EXPLORATORY OBJECTIVES:

I. To explore potential biomarkers, next generation T cell receptor (TCR) sequencing will be performed to identify and longitudinally track individual T cell clones thus granting a comprehensive insight into immunological changes that occur within the tumor and peripheral blood throughout the course of the disease.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive nivolumab intravenously (IV) over 30 minutes at week 0. Treatments repeat every 4 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Beginning week 2, patients also receive radiation therapy on Monday-Friday or 5 days per week for 6 weeks in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes at week 0. Treatments repeat every 2 weeks for nivolumab and 6 weeks for ipilimumab for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer

Randomized, Multi-Institutional Pilot Study of Nivolumab and Radiation Therapy Versus Nivolumab and Ipilimumab as Adjuvant Therapy for Merkel Cell Carcinoma

TT cell analysis will be performed using peripheral blood at regular time points during the study period

Will be estimated along with the 95% confidence interval for each arm based on the binomial distribution.

Kaplan-Meier curves will be generated to summarize the secondary outcomes, RFS and overall survival (OS), for each arm; the differences between groups in terms of hazard ratio for OS/RFS will also be estimated.

Kaplan-Meier curves will be generated to summarize the secondary outcomes, RFS and OS, for each arm; the differences between groups in terms of hazard ratio for OS/RFS will also be estimated.

Adverse experiences will be graded and recorded throughout the study and during the follow-up period according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Side effects will be summarized by each treatment group.

Claire Verschraegen

Principal Investigator

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Urinary Bladder Neoplasms

Melanoma

Carcinoma, Renal Cell

Disease Progression

Melanoma, Cutaneous Malignant

Skin Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Kidney Neoplasms

Kidney Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Pembrolizumab

Avelumab

Immunomodulating Agents

Durvalumab

Atezolizumab

Immunoglobulin G

Immunoglobulins, Intravenous

Immunologic Factors

Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients receive plinabulin IV over 30-60 minutes on days 1 and 4 of cycle 1, days 1 and 4 of cycle 2 (if receiving radiation therapy in cycle 2), and day 1 and or 15 (any day receiving immunotherapy) of subsequent cycles. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.

Plinabulin

Siqing Fu, MD,PHD

Siqing Fu, MD, PHD

This phase Ib/II trial studies the side effects and best dose of plinabulin in combination with radiation therapy and immunotherapy in patients with select cancers that have spread to other places in the body (advanced) after progression on PD-1 or PD-L1 targeted antibodies. Plinabulin blocks tumor growth by targeting both new and existing blood vessels going to the tumor as well as killing tumor cells. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving plinabulin in combination with radiation therapy and immunotherapy may work better in treating advanced cancers.

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability of plinabulin when administered in combination with radiation/immunotherapy regimen in subjects with select advanced solid malignancies after progression on anti-PD-1/PD-L1 monoclonal antibody (mAb).

II. To assess the objective tumor response rate (complete response + partial response).

SECONDARY OBJECTIVES:

I. To assess disease control rate (complete response, partial response + stable disease).

II. To determine progression-free survival (PFS). III. To assess overall survival.

EXPLORATORY OBJECTIVES:

I. To analyze the gene mutation density within each sample. II. To assess T-cell receptor (TCR) sequencing in tumor tissue and peripheral blood, pre- and post- treatment.

III. To perform imaging mass flow cytometry (CyTOF) and/or single cell ribonucleic acid sequencing (RNAseq) analysis on tumor tissue: Immune phenotyping, including dendritic cell (DC), T cells, tumor-associated macrophage (TAM)s, pre and post treatment.

IV. To conduct phenotyping analysis of immune cells from peripheral blood using multicolor flow cytometry.

V. To evaluate dendritic cell activation from whole blood upon the treatment. VI. To explore general predictive and response biomarker measurements from the collected biomarkers.

OUTLINE: This is a phase Ib, dose-escalation study of plinabulin followed by a phase II study. Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients receive plinabulin intravenously (IV) over 30-60 minutes on days 1 and 4 of cycle 1, days 1 and 4 of cycle 2 (if receiving radiation therapy in cycle 2), and day 1 and or 15 (any day receiving immunotherapy) of subsequent cycles. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients undergo radiation therapy on days 1-3, 1-4, or 1-5 of cycle 1. Patients may undergo additional radiation in cycle 2 at the discretion of treating physician. Patients also receive immunotherapy consisting of either: avelumab IV over 1 hour on days 1 and 15; atezolizumab over 30-60 minutes on day 1; durvalumab IV over 1 hour on days 1 and 15; nivolumab IV over 30-60 min on days 1 and 15; or pembrolizumab IV over 30 min on day 1. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 12 months.

Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies

An Open-label, Single-Center, Phase 1b/2 Study to Evaluate the Safety of Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Malignancies After Progression on PD-1 or PD-L1 Targeted Antibodies

AEs will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Radiologic evaluations will be performed at screening and every 9 weeks (± 1 week) for 27 weeks (during Q3W dosing) or every 8 weeks (± 1 week) for 24 weeks (during Q4W dosing), then every 12 weeks during treatment cycles in the Treatment Phase regardless of treatment cycles and follow up period. Categorization of response will be based on both immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) and modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

Will be analyzed using Kaplan-Meier method or Cox regression.

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer	NCT03798639	Merkel Cell Car... Pathologic Stag... Pathologic Stag...	Ipilimumab Nivolumab Radiation Thera...	18 Years -	Ohio State University Comprehensive Cancer Center
Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies	NCT04902040	Advanced Bladde... Advanced Lung N... Advanced Malign... Advanced Melano... Advanced Merkel... Advanced Renal ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Stage III Bladd... Stage III Lung ... Stage III Renal... Stage IIIA Blad... Stage IIIA Lung... Stage IIIB Blad... Stage IIIB Lung... Stage IIIC Lung... Stage IV Bladde... Stage IV Lung C... Stage IV Renal ... Stage IVA Bladd... Stage IVA Lung ... Stage IVB Bladd... Stage IVB Lung ...	Atezolizumab Avelumab Durvalumab Nivolumab Pembrolizumab Plinabulin Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies	NCT04902040	Advanced Bladde... Advanced Lung N... Advanced Malign... Advanced Melano... Advanced Merkel... Advanced Renal ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Stage III Bladd... Stage III Lung ... Stage III Renal... Stage IIIA Blad... Stage IIIA Lung... Stage IIIB Blad... Stage IIIB Lung... Stage IIIC Lung... Stage IV Bladde... Stage IV Lung C... Stage IV Renal ... Stage IVA Bladd... Stage IVA Lung ... Stage IVB Bladd... Stage IVB Lung ...	Atezolizumab Avelumab Durvalumab Nivolumab Pembrolizumab Plinabulin Radiation Thera...	18 Years -	M.D. Anderson Cancer Center
Nivolumab and Radiation Therapy or Ipilimumab as Adjuvant Therapy in Treating Patients With Merkel Cell Cancer	NCT03798639	Merkel Cell Car... Pathologic Stag... Pathologic Stag...	Ipilimumab Nivolumab Radiation Thera...	18 Years -	Ohio State University Comprehensive Cancer Center

Spots Global Cancer Trial Database for pathologic stage iiib merkel cell carcinoma ajcc v8