Neoplasms

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

All Conditions

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Infections

Rare Diseases

Nasopharyngeal Carcinoma

Recurrence

Carcinoma

Carcinoma, Neuroendocrine

Adenocarcinoma

Carcinoma, Squamous Cell

Neuroendocrine Tumors

Mesothelioma

Mesothelioma, Malignant

Carcinoma, Merkel Cell

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Neoplasms, Squamous Cell

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Adenoma

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Communicable Diseases

Polyomavirus Infections

Virus Diseases

DNA Virus Infections

Tumor Virus Infections

Neuroendocrine Tumor

Malignant Mesothelioma

Penile Cancer

Pancreatic Neuroendocrine Tumor

Adenocarcinoma of the Appendix

Merkel Cell Carcinoma

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Bevacizumab

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

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.

Laboratory Biomarker Analysis

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.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Nivolumab

Patients receive nivolumab IV over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Brigette B Ma

This phase II trial studies how well nivolumab works in treating patients with nasopharyngeal cancer that has returned after a period of improvement (recurrent) and/or has spread to other parts of the body (metastatic). Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

PRIMARY OBJECTIVES:

I. Objective tumor response to nivolumab in patients with previously treated recurrent and/or metastatic nasopharyngeal carcinoma (NPC) based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.

SECONDARY OBJECTIVES:

I. Tumor response to nivolumab based on immune-related response criteria (IRC). II. Duration of response. III. Progression-free survival and overall survival. IV. Safety and tolerability.

TERTIARY OBJECTIVES:

I. To investigate the effect of nivolumab on tumor burden by analyzing the clearance of plasma Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) during the first 4-6 weeks of treatment.

II. To investigate the association between treatment outcome and immunological markers: a) Intratumoral expression of programmed cell death 1 (PD-1) and programmed cell death-ligand (PD-L1) in archived NPC tissues (mandatory); b) Serum absolute lymphocyte count at baseline and post-treatment (mandatory); and c) Plasma cytokine levels at baseline and serially during the first 8 weeks of treatment; d) Expression of PD-1 in cluster of differentiation (CD)8+ T cells in tumor infiltrating lymphocytes (TIL) at baseline (optional).

III. To investigate functional magnetic resonance imaging (MRI) sequences as an early predictor of response to nivolumab (optional only at Chinese University of Hong Kong \[CUHK\]).

OUTLINE:

Patients receive nivolumab intravenously (IV) over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 3 years.

Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer

Multicenter Phase II Study of Nivolumab in Previously Treated Patients With Recurrent and Metastatic Nasopharyngeal Carcinoma

Plasma EBV DNA half-life during the first 6 weeks of treatment will be correlated with RECIST-response to nivolumab.

PD-1 and PD-L1 expression will be associated with treatment outcomes. The Chi-Square (or Fisher's Exact test) will be used to assess the association of categorical clinical data with categorical biomarker data. Time-to-event clinical data (PFS, OS) will be correlated with biomarker data using Kaplan-Meier methodology and Cox regression models. Logistic regression models will also be used to predict binary clinical data with baseline biomarker data. Finally, graphical methods and descriptive statistics will be used to summarize the data as well.

The Chi-Square (or Fisher's Exact test) will be used to assess the association of categorical clinical data with categorical biomarker data. Time-to-event clinical data (PFS, OS) will be correlated with biomarker data using Kaplan-Meier methodology and Cox regression models. Logistic regression models will also be used to predict binary clinical data with baseline biomarker data. Finally, graphical methods and descriptive statistics will be used to summarize the data as well.

Graphical methods and descriptive statistics will be used.

Confirmed response rate is defined as either a Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1. \> To be consider a CR, there must be a disappearance of all target lesions and each target lymph node must have reduction in short axis to \< 1.0 cm.\> \> To be considered a PR, at least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline value.\>

\> The confirmed response rate is reported as the number of patients reporting a CR or PR divided by the total number of evaluable patients multiplied by 100 (reported as a percentage).

Adverse events were collected and recorded according to the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. For this outcome measure, we summarize the worst graded adverse event regardless of treatment attribution per patient. All reported adverse events are reported in the Adverse Events section of this report.

The Immune Response Criteria (IRC) is a response criteria derived from the WHO criteria.

Duration of response defined as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed according to RECIST version 1.1.

Progression Free Survival is defined as the time from registration to the time of death or progression, whichever occurs first. The distribution of PFS will be estimated using the method of Kaplan-Meier.

Overall survival is defined as the time from registration to the time of death. The distribution of survival time will be estimated using the method of Kaplan-Meier.

Adverse events were recorded after every 28 day cycle, up to 42 cycles.

Patients receive 3 mg/kg nivolumab IV over approximately 60 minutes on days 1 and 15. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Treatment (Nivolumab)

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Singapore

United States

China

Region of Enrollment

All patients that registered for protocol treatment are included in this analysis.

Brigette B.Y. Ma

One patient was a protocol violation and was not included in this analysis.

Confirmed Response Rate (Complete Response or Partial Response) Based on RECIST Version 1.1

Grade 3 or higher

Grade 4 or higher

Grade 5

All patients that began protocol treatment are included in this analysis.

Adverse Events

Data was not collected to analyze this secondary endpoint.

Tumor Response to Nivolumab Based on the Immune Response Criteria (IRC)

All patients that reported a CR or PR on treatment were included in this analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer	NCT02339558	Nasopharyngeal ... Recurrent Nasop... Stage III Nasop... Stage IV Nasoph... Stage IVA Nasop... Stage IVB Nasop... Stage IVC Nasop...	Laboratory Biom... Nivolumab	18 Years -	National Cancer Institute (NCI)
Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer	NCT02339558	Nasopharyngeal ... Recurrent Nasop... Stage III Nasop... Stage IV Nasoph... Stage IVA Nasop... Stage IVB Nasop... Stage IVC Nasop...	Laboratory Biom... Nivolumab	18 Years -	National Cancer Institute (NCI)
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

Spots Global Cancer Trial Database for stage iii nasopharyngeal carcinoma ajcc v7