Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Carboplatin

Bevacizumab

Pemetrexed

Cisplatin

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Immune Checkpoint Inhibitors

Immunologic Factors

Folinic Acid

Folate

Vitamin B9

4 cycles of induction every 3 weeks with :

* Carboplatin area under curve 6 mg/mL per minute per IV route or Cisplatin 75 mg/m² per IV route
* Pemetrexed 500 mg/m² per IV route
* Atezolizumab 1200 mg per IV route
* Bevacizumab 15 mg/kg per IV route For patients without disease progression, treatment will be followed by maintenance therapy by Atezolizumab + Pemetrexed and Bevacizumab administered at the same dosage on 3-week cycles

4 cycles of induction every 3 weeks with :

* Carboplatin area under curve 6 mg/mL per minute per IV route or Cisplatin 75 mg/m² per IV route
* Pemetrexed 500 mg/m² per IV route
* Atezolizumab 1200 mg per IV route For patients without disease progression, treatment will be followed by maintenance therapy by Atezolizumab + Pemetrexed administered at the same dosage on 3-week cycles

4 cycles of induction every 3 weeks of cisplatine,pemetrexed, atezolizumab + bevacizumab and patients without disease progression, treatment will be followed by maintenance therapy by Atezolizumab + Pemetrexed +/- Bevacizumab administered at the same dosage on 3-week cycles

Carboplatin + Pemetrexed + Atezolizumab + Bevacizumab

Carboplatin + Pemetrexed + Atezolizumab

BYLICKI Olivier, MD

GRELLARD Jean-Michel, Project manager

JUSTEAU Gregoire, MD

HOMINAL Stéphane, MD

DESCOURT Renaud, MD

Sebastien COURAUD, PhD

GERVAIS Radj, MD

GRELLARD Jean-Michel

JANICOT Henri, MD

MONNET Isabelle, MD

MORO-SIBILOT Denis, PhD

Acya BIZIEUX, MD

Diane MOREAU, MD

Eric HUCHOT, MD

Alexis CORTOT, MD

VERGNENEGRE Alain, PhD

PEROL Maurice, MD

GREILLER Laurent, PhD

Hugues MOREL, MD

DOUBRE Helene, MD

DANIEL Catherine, MD

VEILLON Rémi, MD

COURAUD Sébastien, MD

LENA Hervé, MD

BOTA Suzanna, MD

FOURNEL Pierre, PhD

SCHOTT Roland, MD

PALEIRON Nicolas, MD

BIGAY GAME Laurence, MD

Gonzague DE CHABOT, MD

ARPIN Dominique, MD

PELONI Jean-Michel, MD

The objective of this study is to assess the efficacy of the combination of Platinum (carboplatin or cisplatin), Pemetrexed, Atezolizumab+/- Bevacizumab if eligible, in stage IIIB/IV non-squamous non-small cell lung cancer patients with progression-enhancing mutations following targeted therapies.

In patients with an EGFR mutation, several phase III studies comparing EGFR tyrosine kinase inhibitors (TKIs) with chemotherapy have shown a benefit of TKI over chemotherapy, with no demonstrated benefit on overall survival. After a first line of treatment with a TKI, most patients progress and are eligible according to the mechanism of progression to a TKI of 3rd generation in case of T790M resistance or chemotherapy. In patients with ALK translocation, crizotinib has been shown to be beneficial in first line compared to a platinum doublet.Despite these major advances, most patients are progressing after targeted treatments and chemotherapy and are facing the problem of anti-PD1 / PDL1 treatment.

Open-label, multicentre, non-randomized two parallel cohorts phase II study

A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies

A Multicentre Phase II, Open-label, Non-randomized Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/- Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies

GFPC

Centre Francois Baclesse

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

Subjects who, at enrollment, have been on a TKI for less than 4 weeks will be monitored with the Sensus smartphone application, Fitbit Sense, RX Cap, and paper surveys. Visits will be at: Screening, Baseline, 1 Week, 2 Weeks, 4 Weeks, 8 Weeks, 16 weeks, and 24 weeks.

Subjects who, at enrollment, have been on a TKI for 4 weeks or more will be monitored with the Sensus smartphone application, Fitbit Sense, RX Cap, and paper surveys. Visits will be at: Screening, Baseline, Week 1, and then every 8 weeks for 24 weeks.

Sensus is capable of administering ecological momentary assessments (EMAs) on a schedule, randomly, or using sensor-triggers. In this way, Sensus will capture both active (patient-initiated) and passive data streams from native smartphone sensors. Passive streams may include, but are not limited to, GPS, accelerometer, gyroscope, and pedometer data. Participants will be able to log data such as their activity, symptoms and medication adherence via user-initiated surveys within the Sensus app. Sensus will also prompt users to record their medication adherence, symptoms, or activity. This will be done either at fixed intervals (e.g., three times daily) or whenever the onboard sensors detect potential changes in a user's physiological state (e.g., shaking / moving around).

Sensus Smartwatch Application

The RXCap medication event monitoring device will be used to collect data on participant adherence to their TKI medication. A small computer chip is included in the top of a pill bottle. When the cap is taken off of the pill bottle by turning it or unscrewing it, the cap records the time and date that it was removed.

RX Cap

The Fitbit Sense smartwatch will be used to collect data including steps, calories burned, total distance travelled, sleep (e.g. time spent sleeping and quality of sleep), flights of stairs climbed, active minutes, exercise (e.g. minutes spent exercising at various intensities), and average heart rate.

Fitbit Sense

Electronic and paper surveys will be administered throughout the study.

Surveys

Ryan Gentzler, MD

In this study, patients who are taking oral tyrosine kinase inhibitor (TKI) therapy for lung cancer will be asked to participate in a remote monitoring system for up to 24 weeks. The system will include:

* a smartphone application (app) developed at the University of Virginia called Sensus. Sensus will be downloaded to the participant's smartphone. The app will collect active data (such as through surveys) and passive data (such as accelerometer data).
* a fitness watch called a Fitbit will be given to the participant to be used during the study. The Fitbit will collect information such as steps and average heart rate.
* a smart pill cap called RX Cap will be given to the participant to be used during the study. The pill cap will collect information about how often a pill bottle is opened.

The study will also involve paper surveys that are taken by the participant during clinic visits. Symptoms related to TKI therapy will be recorded by an investigator in the clinic.

The study results will be used to guide development of a real-time symptom monitoring system, with the ultimate goal of improving TKI symptom response and quality of life.

This is a prospective pilot study for adult patients with lung cancer who have tumors harboring an actionable mutation and who are undergoing treatment with oral tyrosine kinase inhibitors (TKIs). The choice and dose of TKI will be at the discretion of the treating medical oncologist. The study will assess symptoms and adverse events using a remote monitoring system that uses brief self-report surveys and passive input from smart devices as well as clinical assessment of adverse events and quality of life during routine office visits. An application loaded onto a smart phone (Sensus) and a fitness tracking device (Fitbit Sense) will capture information about symptoms and adverse events. This information will be captured through surveys and from passive input from the smart devices. Surveys will also be used to capture the subjects' experience with the devices. The results of this pilot study will be used to guide future development of a mobile health system application for remote real-time symptom monitoring to implement earlier interventions to reduce severity of symptoms, improve quality of life, and avoid drug discontinuations and dose reductions in this patient population.

Real-Time Monitoring of Symptoms in Lung Cancer Patients Receiving Oral Targeted Therapies

Real-Time Monitoring and Modeling of Symptoms and Adverse Events in Lung Cancer Patients Receiving Oral Targeted Therapies for Tumors With Actionable Mutations

Number of participants wearing the device and responding to remote electronic surveys at least 50% of the time.

Adverse event frequency and severity recorded by the app and from in-person clinical assessments using the CTCAE v5.

University of Virginia

Principal Investigator

Neoplasms, Second Primary

Patients receive brigatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

90 mg orally QD for 7 days followed by 180 mg orally QD continuously thereafter. One cycle of therapy will consist of 28 days of treatment.

Brigatinib

Laboratory Biomarker Analysis

Quality-of-Life Assessment

Questionnaire Administration

Sameek Roychowdhury, MD

This phase II trial studies how well brigatinib works in treating patients with ALK and ROS1 gene alterations and solid cancers that have spread to nearby tissue and lymph nodes or other places in the body. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. To evaluate the overall response rate (ORR) of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors).

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors).

II. To assess progression free survival (PFS) and overall survival (OS) in patients with advanced ALK or ROS1 mutated solid tumors treated with brigatinib.

III. To assess sensitivity and durability of response to brigatinib in different solid tumor types.

IV. To assess the role of intertumoral and intratumoral heterogeneity in the development of resistance to brigatinib.

V. To identify candidate genomic (including circulating tumor deoxyribonucleic acid \[DNA\]) and proteomic biomarkers of tumor sensitivity and resistance to brigatinib using high-throughput approaches (exome, transcriptome, reverse phase protein array \[RPPA\]).

TERTIARY OBJECTIVES:

I. Correlation of brigatinib exposure with efficacy and safety. II. Correlation of tumor and plasma biomarkers with brigatinib efficacy and safety.

OUTLINE:

Patients receive brigatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 52 weeks.

Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers

Phase II Study of Brigatinib for Advanced Solid Cancers Harboring Genomic Alterations in ALK (Excluding Lung) and ROS1 Oncogenes

Brigatinib exposure will be compared to RECIST measurements and adverse events measured using CTCAE v4.

Correlative and protein markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. response vs. no response). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement (e.g. response versus no response). Will correlate with efficacy and safety.

Response for tumors will be assessed using the RECIST 1.1 criteria (using computed tomography scans or calipers by clinical exam) where response will be defined as a partial or complete response. Will be calculated with 95% binomial confidence intervals for the estimate of the proportion of responses.

Will be assessed by central independent review committee per RECIST version 1.1.

Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Kaplan-Meier curves will be used to estimate the survival distributions of overall survival.

Kaplan-Meier curves will be used to estimate the survival distributions of progression-free survival.

Will be calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for clinical benefit rate will be calculated.

The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset.

The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset. Genes will be evaluated in aggregate from whole exome and transcriptome sequencing.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies	NCT04042558	NSCLC Stage III... NSCLC Stage IV EGFR Gene Mutat... ALK Gene Rearra... ROS1 Gene Mutat...	Carboplatin + P... Carboplatin + P...	18 Years - 75 Years	Centre Francois Baclesse
Real-Time Monitoring of Symptoms in Lung Cancer Patients Receiving Oral Targeted Therapies	NCT05370469	Lung Cancer EGFR Gene Mutat... EGFR ALK Gene Mutati... RET Gene Mutati... MET Gene Mutati... KRAS Mutation-R... BRAF ROS1 Gene Mutat...	Sensus Smartwat... RX Cap Fitbit Sense Surveys	18 Years -	University of Virginia
Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers	NCT03868423	Advanced Malign... ALK Fusion Prot... ALK Gene Amplif... ALK Gene Mutati... Locally Advance... Metastatic Mali... Metastatic Mali... Metastatic Mali... ROS1 Fusion Pos... ROS1 Gene Ampli... ROS1 Gene Mutat...	Brigatinib Laboratory Biom... Quality-of-Life... Questionnaire A...	18 Years -	Ohio State University Comprehensive Cancer Center
A Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/-Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressing After Targeted Therapies	NCT04042558	NSCLC Stage III... NSCLC Stage IV EGFR Gene Mutat... ALK Gene Rearra... ROS1 Gene Mutat...	Carboplatin + P... Carboplatin + P...	18 Years - 75 Years	Centre Francois Baclesse

Spots Global Cancer Trial Database for ros1 gene mutation