Neoplasms

All Conditions

Infections

Symptoms and General Pathology

Rare Diseases

Carcinoma

Communicable Diseases

Carcinoma, Merkel Cell

Polyomavirus Infections

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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

Anti-Infective Agents

Antibodies

Avelumab

Immunomodulating Agents

Immunoglobulins

Interferons

Interferon-beta

Antibodies, Monoclonal

Antiviral Agents

Antineoplastic Agents, Immunological

Immunologic Factors

Patients who do not have a HLA type for which T cells can be generated or for whom T cells cannot be generated for technical issues receive avelumab intravenously (IV) over 1 hour every 2 weeks for 12 months. Within 7-10 days after completion of 1-3 doses of avelumab, patients receive MHC class I up-regulation intervention comprising either localized radiation therapy or recombinant interferon beta via intra-tumor injection.

Patients who have an HLA type for which T cells can be generated receive avelumab IV over 1 hour every 2 weeks for 12 months. Patients also receive MHC class I up-regulation intervention as in Group 1 between 7-10 days after the first infusion of avelumab and 2-5 days before the first infusion of MCPyV TAg-specific polyclonal autologous CD8+ T cells. Patients receive two infusions of MCPyV TAg-specific polyclonal autologous CD8+ T cells IV over 60-120 minutes.

Laboratory Biomarker Analysis

MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells

Radiation Therapy

Recombinant Interferon Beta

Aude Chapuis

This phase I/II trial studies the side effects and how well localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy works in treating patients with Merkel cell carcinoma that has spread to other parts of the body. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Interferon beta is a substance that can improve the body's natural response and may interfere with the growth of tumor cells. Monoclonal antibodies, such as avelumab, may help T lymphocytes kill tumor cells. For cellular adoptive immunotherapy, specific white blood cells are collected from the patient's blood and treated in the laboratory to recognize Merkel cell carcinoma. Infusing these cells back into the patient may help the body build an effective immune response to kill Merkel cell carcinoma. Giving localized radiation therapy or recombinant interferon beta and avelumab with or without cellular adoptive immunotherapy may be a better treatment for Merkel cell carcinoma.

PRIMARY OBJECTIVES:

I. Assess and compare the safety and potential toxicities associated with treating patients with metastatic Merkel cell carcinoma (MCC) with either major histocompatibility complex (MHC) up regulation and programmed cell death 1 (PD1)-axis blockade (Group 1), or MHC up-regulation, PD1-axis blockade and adoptive transfer of Merkel cell polyoma virus (MCPyV) T antigen (TAg)-specific polyclonal autologous cluster of differentiation (CD)8+ T cells (Group 2).

II. Assess and compare the antitumor efficacy associated with treating patients with metastatic MCC with either MHC up-regulation and PD1-axis blockade (Group 1), or MHC up-regulation, PD1-axis blockade and adoptive transfer of MCPyV TAg-specific polyclonal autologous CD8+ T cells (Group 2).

SECONDARY OBJECTIVES:

I. Examine the in vivo persistence and, where evaluable, migration to tumor sites of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV TAg (Group 2).

II. Examine the in vivo functional capacity of adoptively transferred polyclonal CD8+ T cells targeting the MCPyV Tag (Group 2).

III. Examine and compare evidence of epitope spreading with either MHC up-regulation and adoptive transfer of MHC up-regulation and PD1-axis blockade (Group 1), or MHC up regulation, PD1-axis blockade and adoptive transfer of MCPyV TAg-specific polyclonal autologous CD8+ T cells (Group 2).

OUTLINE: Patients are assigned to 1 of 2 groups.

GROUP 1: Patients who do not have a human leukocyte antigen (HLA) type for which T cells can be generated or for whom T cells cannot be generated for technical issues receive avelumab intravenously (IV) over 1 hour every 2 weeks for 12 months. Within 7-10 days after completion of 1-3 doses of avelumab, patients receive MHC class I up-regulation intervention comprising either localized radiation therapy or recombinant interferon beta via intra-tumor injection.

GROUP 2: Patients who have an HLA type for which T cells can be generated receive avelumab IV over 1 hour every 2 weeks for 12 months. Patients also receive MHC class I up-regulation intervention as in Group 1 between 7-10 days after the first infusion of avelumab and 2-5 days before the first infusion of MCPyV TAg-specific polyclonal autologous CD8+ T cells. Patients receive two infusions of MCPyV TAg-specific polyclonal autologous CD8+ T cells IV over 60-120 minutes.

In both groups, MHC class I up-regulation treatment with or without T cell infusions may repeat if indicated.

After completion of study treatment, patients are followed up at 12 months and then periodically thereafter.

Localized Radiation Therapy or Recombinant Interferon Beta and Avelumab With or Without Cellular Adoptive Immunotherapy in Treating Patients With Metastatic Merkel Cell Carcinoma

Study to Evaluate Cellular Adoptive Immunotherapy Using Polyclonal Autologous CD8+ Antigen-Specific T Cells for Metastatic Merkel Cell Carcinoma in Combination With MHC Class I Up-Regulation and the Anti-PD-L1 Antibody Avelumab

Median time to new metastases reported for each group below. Group 1 result is NA, patient had no new detectable metastases in study follow-up period. Arm I is not analyzed because the one patient in Arm I did not experience new metastasis in their followup period, so they are not evaluable.

Evidence and nature of toxicity related to the treatment will be assessed and compared between groups.

Patients were evaluated for their disease response throughout their follow up period. Disease response reported is best response per patient. A complete response (CR) will be defined as total regression of all tumors, a PR as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and PD as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter (RECIST v1.1 criteria).

Quantiﬁcation of the overall recognition of the MCPyV T-antigen for each patient will likely be performed by testing the reactivity of whole peripheral blood mononuclear cells (PBMC) before and at indicated timepoints after treatment to peptides 15 amino acids (aa) in length offset by 5 aa bases spanning the whole T-antigen protein to include both CD8 and CD4 responses regardless of the HLA type of the patient. Due to changes in assay technology, epitope spreading was detected using a flow cytometric based intracellular cytokine assay.

To evaluate the direct ex vivo function of the transferred cells, where possible, tetramer+ cells within collected peripheral blood mononuclear cells (PBMCs) will be evaluated for production of intracellular cytokines including interferon (IFN), tumor necrosis factor alpha and interleukin-2 in response to cognate antigen using an intracellular cytokine assay. This endpoint was evaluable in 4 of 7 patients, all 4 of whom upregulated interferon, tumor necrosis factor alpha and IL-2 expression in response to cognate antigen using intracellular cytokine assay. Persistence was not detected for 3 out of 7 patients in group 2, making them unevaluable for functional capacity.

Survival status in patients with Merkel cell carcinoma will be evaluated. Data is reported as count of participants that survived past the 1 year follow up period.

Persistence of trasferred T cells was evaluated and assessed after 90 days. Patients were counted if transferred T cells were detected beyond 90 days.

EMD Serono

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

Associate Professor

All unexpected and serious AEs which may be due to study treatment or intervention must be reported to the FHCRC Institutional Review Office (IRO) per their current reporting requirements.

All grade ≥ 3 CTCAE v.4 AEs will be collected through 4 weeks after each participant's last T-cell infusion and per section 12.C. Beginning 4 weeks after the participant's last infusion, only study related toxicities will be collected.ci

Patients who do not have a HLA type for which T cells can be generated or for whom T cells cannot be generated for technical issues receive avelumab intravenously (IV) over 1 hour every 2 weeks for 12 months. Within 7-10 days after completion of 1-3 doses of avelumab, patients receive MHC class I up-regulation intervention comprising either localized radiation therapy or recombinant interferon beta via intra-tumor injection.

Avelumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

Radiation Therapy: Undergo radiation therapy

Recombinant Interferon Beta: Given via intra-tumor injection

Group 1 (Avelumab and MHC Class I Up-regulation)

Patients who have an HLA type for which T cells can be generated receive avelumab IV over 1 hour every 2 weeks for 12 months. Patients also receive MHC class I up-regulation intervention as in Group 1 between 7-10 days after the first infusion of avelumab and 2-5 days before the first infusion of MCPyV TAg-specific polyclonal autologous CD8+ T cells. Patients receive two infusions of MCPyV TAg-specific polyclonal autologous CD8+ T cells IV over 60-120 minutes.

Avelumab: Given IV

Laboratory Biomarker Analysis: Correlative studies

MCPyV TAg-specific Polyclonal Autologous CD8-positive T Cells: Given IV

Radiation Therapy: Undergo radiation therapy

Recombinant Interferon Beta: Given via intra-tumor injection

Group 2 (Avelumab, MHC Class I Up-regulation, T Cells)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Aude Chapuis

Patient in group 1 did not experience new metastasis in followup period of 1 year. Only 4 patients in group 2 experienced new metastases in the followup period of 1 year. The other 3 patients in group 2 were omitted due to no new metastases.

Evidence of Response, Based on Median Time to New Metastasis

Count of Participants Who Experienced Adverse Events, Evaluated According to the Current Guidelines in National Cancer Institute (NCI) Common Toxicity Criteria Version 4.0

Disease Response, as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1

Count of Participants That Displayed Evidence of Epitope Spreading

Functional Capacity of Transferred T Cells (Group 2)

Merkel Cell Carcinoma (MCC)-Specific Survival

Count of Participants Who Displayed Persistence of Transferred T Cells in Blood and Tumor (Group Co2)

Overall Study

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Nasopharyngeal Carcinoma

Recurrence

Carcinoma, Squamous Cell

Mesothelioma

Mesothelioma, Malignant

Lung Neoplasms

Disease Attributes

Neoplasms, Squamous Cell

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Adenoma

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Penile Cancer

Pancreatic Neuroendocrine Tumor

Adenocarcinoma of the Appendix

Bevacizumab

Atezolizumab

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

Patients receive atezolizumab and bevacizumab IV over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Pharmacological Study

Daniel M Halperin, MD

This phase II trial studies how well atezolizumab and bevacizumab work in treating patients with rare solid tumors. Immunotherapy with monoclonal antibodies, such as atezolizumab and bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of atezolizumab when given in combination with bevacizumab (atezo bev).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of atezo bev. II. To evaluate the safety of atezo + bev.

EXPLORATORY BIOMARKER OBJECTIVES:

I. To identify biomarkers that are predictive of response to atezo bev (i.e., predictive biomarkers), are associated with progression to a more severe disease state (i.e., prognostic biomarkers), are associated with resistance to atezo bev, are associated with susceptibility to developing adverse events, can provide evidence of study treatment activity, or can increase the knowledge and understanding of disease biology.

OUTLINE:

Patients receive atezolizumab and bevacizumab intravenously (IV) over 60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors

A Phase II, Single-Arm Open-Label Study of the Combination of Atezolizumab and Bevacizumab in Rare Solid Tumors

The relationship between biomarkers in blood and tumor tissue and efficacy, safety, pharmacokinetics, immunogenicity, or other biomarker endpoints will be assessed. Summary statistics for biomarkers and their corresponding changes (or percent changes) from baseline will be tabulated by planned study day and dose in each tumor group. The time-course of biomarker measures will be investigated graphically. If there is indication of meaningful pattern over time, further analysis (eg, by linear mixed model) may be performed to characterize the relationship. Methods such as, but not limited to, logistic regression will be used to explore possible associations between biomarker measures and clinical outcomes.

Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (modified RECIST for pleural mesothelioma). Will be defined as a complete response or partial response on two consecutive occasions 4 weeks apart as determined by an independent radiologist. For each tumor group, the best response rate and its 95% exact confidence interval will be estimated using the Clopper and Pearson method. The combination treatment will be assessed by performing the independent binomial test comparing the best response rate versus the historical control for each tumor group. The Bayesian classification and information sharing method proposed by Lee and Chen may be applied.

Will be assessed by immune-modified RECIST

Will be assessed by RECIST 1.1 (modified RECIST for pleural mesothelioma). Will be estimated using Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model may be utilized to include multiple covariates in the time-to-event analysis.

Will be assessed by RECIST 1.1 (modified RECIST for pleural mesothelioma). For each tumor group the median duration of response and corresponding 2-sided 95% confidence interval will be reported.

Will be estimated using Kaplan-Meier method. The log-rank test will be performed to test the difference in time-to-event distributions between patient groups. Cox proportional hazards model may be utilized to include multiple covariates in the time-to-event analysis.

Will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Verbatim adverse events and severity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The safety analyses will include all patients who received at least one dose of study treatment. Toxicity data will be summarized by frequency tables for each tumor type group. The association between the types and severity of toxicity and the tumor group will be evaluated. No formal statistical testing will be performed on these summary.

M.D. Anderson Cancer Center

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Localized Radiation Therapy or Recombinant Interferon Beta and Avelumab With or Without Cellular Adoptive Immunotherapy in Treating Patients With Metastatic Merkel Cell Carcinoma	NCT02584829	Merkel Cell Pol... Stage IV Merkel...	Avelumab Laboratory Biom... MCPyV TAg-speci... Radiation Thera... Recombinant Int...	18 Years -	Fred Hutchinson Cancer Center
Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors	NCT03074513	Appendix Adenoc... Human Papilloma... Human Papilloma... Human Papilloma... Human Papilloma... Neuroendocrine ... Pancreatic Neur... Recurrent Merke... Recurrent Nasop... Recurrent Perit... Recurrent Pleur... Stage III Merke... Stage III Nasop... Stage III Pleur... Stage IV Merkel... Stage IV Nasoph... Stage IV Pleura... Stage IVA Nasop... Stage IVB Nasop... Stage IVC Nasop... Vaginal Squamou...	Atezolizumab Bevacizumab Laboratory Biom... Pharmacological...	18 Years -	M.D. Anderson Cancer Center
Atezolizumab and Bevacizumab in Treating Patients With Rare Solid Tumors	NCT03074513	Appendix Adenoc... Human Papilloma... Human Papilloma... Human Papilloma... Human Papilloma... Neuroendocrine ... Pancreatic Neur... Recurrent Merke... Recurrent Nasop... Recurrent Perit... Recurrent Pleur... Stage III Merke... Stage III Nasop... Stage III Pleur... Stage IV Merkel... Stage IV Nasoph... Stage IV Pleura... Stage IVA Nasop... Stage IVB Nasop... Stage IVC Nasop... Vaginal Squamou...	Atezolizumab Bevacizumab Laboratory Biom... Pharmacological...	18 Years -	M.D. Anderson Cancer Center
Localized Radiation Therapy or Recombinant Interferon Beta and Avelumab With or Without Cellular Adoptive Immunotherapy in Treating Patients With Metastatic Merkel Cell Carcinoma	NCT02584829	Merkel Cell Pol... Stage IV Merkel...	Avelumab Laboratory Biom... MCPyV TAg-speci... Radiation Thera... Recombinant Int...	18 Years -	Fred Hutchinson Cancer Center
Localized Radiation Therapy or Recombinant Interferon Beta and Avelumab With or Without Cellular Adoptive Immunotherapy in Treating Patients With Metastatic Merkel Cell Carcinoma	NCT02584829	Merkel Cell Pol... Stage IV Merkel...	Avelumab Laboratory Biom... MCPyV TAg-speci... Radiation Thera... Recombinant Int...	18 Years -	Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for stage iv merkel cell carcinoma ajcc v7