Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma, Hepatocellular

Sarcoma

Melanoma

Sarcoma, Alveolar Soft Part

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Neoplasms, Connective and Soft Tissue

Small Cell Lung Cancer

Soft Tissue Sarcoma

Alveolar Soft Part Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Immunomodulating Agents

Atezolizumab

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Atezolizumab administered via IV at either 1,200 mg q3 weeks, or 1,680 mg q4 weeks for the first 2 doses followed by 850mg q2 weeks or q6 weeks.

NCI Medical Oncology Referral Office

James L Gulley, M.D.

National Cancer Institute Referral Office

Background:

A type of drug called monoclonal antibody immune checkpoint inhibitors are often used in cancer treatment. These drugs help the body s immune system fight cancer by blocking proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved to treat certain cancers. Researchers want to find out if lower doses of this drug might provide the same benefit with fewer adverse effects.

Objective:

To test different doses and timing of atezolizumab for people with cancer.

Eligibility:

People aged 18 years and older with cancer that has spread locally or to other organs. They must be eligible for treatment with the study drug.

Design:

Participants will be screened. They will have blood tests and imaging scans. They will provide a sample of tissue from their tumor.

Atezolizumab is administered through a tube attached to a needle inserted into a vein in the arm. Participants will take this drug alone or combined with other drugs prescribed for their care.

The first 2 treatments will be done per the FDA recommended dose and schedule. Before administering the second dose of the study drug, researchers will check the level of the drug in the participant s blood. Depending on those results, their 3rd dose will be scheduled 2 to 6 weeks later.

For the 3rd dose of the study drug, participants will switch to the FDA minimum dosage. Dosages of any other drugs will not change.

Researchers will continue to test the levels of the drug in participants blood before each treatment for 16 weeks. After that, these levels will be tested every 3 months.

Study treatment may last up to 2 years.

Background:

* The treatment of many cancers has been revolutionized through the use of monoclonal antibody immune checkpoint inhibitor drugs, particularly those that block the interaction of the anti-programmed death-ligand 1 (PD-L1) with the programmed death-1 (PD-1) receptor.
* Atezolizumab was initially tested in a phase 1a multicenter, dose-escalation, and dose- expansion study (NCT01375842) which showed that the drug was well tolerated and produced clinical responses in a variety of tumors.
* The initially approved atezolizumab regimen was 1,200 mg every 3 weeks, but 840 mg every 2 weeks was added based on the data from the TNBC trial (NCT01375842). This was taken further by Morrissey et al., who used population pharmacokinetic (PK) simulations to determine that dosing regimens of 840 mg every 2 weeks and 1,680 mg every 4 weeks are interchangeable with 1,200 every 3 weeks in terms of efficacy, leading the Food and Drug Administration (FDA) to expand the dosing regimens for atezolizumab.
* The standard dosing regimens yield steady-state concentrations greater than 10-fold above the stated minimum effective concentration of 6 g/mL, to ensure adequate exposure for all patients, including patients that may experience lower exposure due to the incidence of anti-drug-antibodies (ADA). Atezolizumab exhibits a flat exposure- response relationship.

Objective:

-To test the feasibility of reducing drug exposure while maintaining plasma drug concentration at or above the expected target trough value during a 16-week study period by using a method for therapeutic drug monitoring of atezolizumab.

Eligibility:

* Age \>= 18 years old.
* Participants with a locally advanced or metastatic cancer who are candidates for treatment with atezolizumab, either alone or in combination with other FDA-approved drug(s).
* Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
* Adequate organ and marrow function.

Design:

* This is a phase I feasibility study of a therapeutic drug monitoring (TDM)-based method for atezolizumab dosing.
* The participants will start with FDA approved dose and frequency of atezolizumab (840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks) selected by their treating physician for the first two doses of the drug per standard of care.
* After the second dose, starting at 3rd dose, the dose of the drug will be switched to 840 mg and will be used going forward in the trial in all participants.
* Prior to each dose, starting at the 2nd dose, a trough will be drawn which will be by the population PK model to predict the timing of the next dose to maintain the atezolizumab target trough for each participant specifically. This will be repeated for the first 16 weeks of treatment.
* After 16 weeks of treatment, the timing of the next dose to maintain the atezolizumab target trough for each participant will be monitored and adjusted (if necessary) every 3 months for each participant until 2 years.

A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

A Feasibility Multicenter Phase I Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

The fraction of participants that can be dosed with 840mg of atezolizumab at less frequent intervals while maintaining a trough PK concentration at or above 6 mg/mL

PK evaluations before every atezolizumab infusion starting from the second dose until 16 weeks after atezolizumab treatment and every 3 months after 16 weeks on treatment.

National Cancer Institute (NCI)

Symptoms and General Pathology

Infections

Wounds and Injuries

Respiratory Aspiration

Pneumonia

Radiation Pneumonitis

Communicable Diseases

Respiratory Tract Infections

Anti-Inflammatory Agents

Respiratory System Agents

Beclomethasone

Glucocorticoids

Hormones

Hormone Antagonists

Anti-Asthmatic Agents

Participants inhaled beclomethasone propionate aerosol daily during chest radical radiotherapy (total dose 60GY).

Participants were not given daily inhalation of beclomethasone propionate when undergoing radical chest radiotherapy (total dose 60GY).

Beclomethasone propionate inhaled twice daily during radiotherapy

Beclomethasone propionate

caicun zhou, phD MD

jie zhang, MD

Radical radiotherapy is the main treatment of locally advanced lung cancer, and radiation pneumonia is the main toxic effects of radiotherapy. Among them, the fatality rate of severe radiation pneumonia can reach 50%, which is very harmful to tumor patients. At present, the treatment mode of radiation pneumonia is very few, and the therapeutic effect is poor. The prevention of radiation pneumonitis may be the best way to reduce the number of patients with Post-radiotherapy pneumonia. Previous small clinical studies have shown that the incidence of radiation pneumonia in inhaled beclomethasone group (2 /28) was significantly lower than that in oral prednisone group (8 /29) during radiotherapy. The purpose of this study was to compare the efficacy and safety of radiotherapy between the therapeutic group (inhaled beclomethasone during radiotherapy) and the control radiotherapy group (patients received radiotherapy only), especially the incidence of radiation-induced pneumonia within half a year.

To compare the incidence of radiation pneumonia, effect and side effects of radiotherapy in lung between beclomethasone inhalation therapeutic group and control radiotherapy group in patients with locally advanced non-small cell lung cancer (NSCLC) during radiotherapy.

Prevention of Locally Advanced NSCLC Radiotherapy Pneumonia by Inhaling Beclomethasone Propionate

A Randomized, Open Phase II Study of the Incidence and Safety of Radiation Pneumonia in Patients With Locally Advanced NSCLC Treated With Beclomethasone Propionate Inhaled During Radical Radiotherapy Compared With Conventional Radiotherapy

evaluated every 6 weeks since the thoracic irradiation began according to the EORTC Quality-of-Life Questionnarire-Lung Cancer 13 Module(EORTC OLO-LC13)

To evaluate the incidence of radiation pneumonia in 36weeks since thoracic irradiation between two groups of patients

To evaluate Objective response rate every 6weeks since thoracic irradiation.

To evaluated in the 36 weeks since the thoracic irradiation began according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Shanghai Pulmonary Hospital, Shanghai, China

Tongji University

Professor, doctor

Nervous System Diseases

Apnea

Sleep Apnea Syndromes

full night polysomnographic study and blood sample to detect some genetic issues

sleep study and blood sample

cases of locally advanced non small cell lung cancer (diagnosed by PET/CT scan and histopathological confirmation) will be screened for sleep disorders by Epworth sleepiness scale then confirmed by full night polysomnographic study. Blood sample to detect some genetic determinants will be withdrawn

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing	NCT06066138	Locally Advance... Metastatic Alve... Locally Advance... Metastatic Non ... Locally Advance... Metastatic Smal... Locally Advance... Metastatic Hepa... Locally Advance... Metastatic Mela...	Atezolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Prevention of Locally Advanced NSCLC Radiotherapy Pneumonia by Inhaling Beclomethasone Propionate	NCT03886441	Locally Advance...	Beclomethasone ...	18 Years - 70 Years	Tongji University
A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing	NCT06066138	Locally Advance... Metastatic Alve... Locally Advance... Metastatic Non ... Locally Advance... Metastatic Smal... Locally Advance... Metastatic Hepa... Locally Advance... Metastatic Mela...	Atezolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Sleep Apnea and Lung Cancer	NCT03741647	Locally Advance...	sleep study and...	-	Zagazig University
A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing	NCT06066138	Locally Advance... Metastatic Alve... Locally Advance... Metastatic Non ... Locally Advance... Metastatic Smal... Locally Advance... Metastatic Hepa... Locally Advance... Metastatic Mela...	Atezolizumab	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Prevention of Locally Advanced NSCLC Radiotherapy Pneumonia by Inhaling Beclomethasone Propionate	NCT03886441	Locally Advance...	Beclomethasone ...	18 Years - 70 Years	Tongji University

Spots Global Cancer Trial Database for locally advanced non small cell lung cancer