Clinical trial NCT03911219: Impact of eHealth Monitoring on Overall Survival in Patients With Metastatic NSCLC / Extensive-stage SCLC / Advanced TNBC Under First-line Treatment With Atezolizumab Plus Chemotherapy
Official title: Multicenter Study to Evaluate the Impact of eHealth Monitoring on Overall Survival in Patients With Metastatic Non-squamous NSCLC or Extensive-stage SCLC or Advanced TNBC Under First-line Treatment With Atezolizumab in Combination With Chemotherapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stage IV Non-small Cell Lung Cancer
Extensive-stage Small Cell Lung Cancer
Advanced (Locally Advanced and Inoperable or Metastatic), PD-L1 IC-positive TNBC
Lead sponsor: iOMEDICO AG
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2019-04-11
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Eligible are patients with histologically or cytologically confirmed stage IV NSCLC or extensive-stage SCLC who have already been scheduled to receive first-line treatment with atezolizumab in combination with platinum-based chemotherapy induction followed by atezolizumab-containing maintenance therapy according to the German SmPC (Fachinformation) OR patients with advanced (locally advanced and inoperable or metastatic), PD-L1 IC-positive TNBC who have been scheduled for first-line treatment with atezolizumab in combination with nab-paclitaxel according to the German SmPC (Fachinformation).

Brief summary: The current study is aimed to test the benefit of a web-based application tool in NSCLC, SCLC and TNBC patients during the recently approved first-line treatment strategy with atezolizumab in combination with chemotherapy.

Detailed description: Checkpoint inhibitors represent new, promising treatment opportunities in the palliative lung cancer setting. Among programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) inhibitors, atezolizumab (Tecentriq® ), a PD-L1 inhibitor, has been shown to ameliorate outcomes for NSCLC patients with metastatic disease: The open-label phase II multicenter studies POPLAR and BIRCH revealed an improved overall response rate and a benefit in overall survival (OS) under atezolizumab monotherapy. The open-label, randomized phase III OAK trial led to atezolizumab approval as monotherapy for patients with metastatic NSCLC whose disease progressed during or following platinumcontaining chemotherapy regardless of PD-L1 status.

Despite these developments, platinum-based chemotherapy regimens are still standard of care for lung cancer without druggable alterations. Lately combining conventional chemotherapeutics with immunotherapy showed promising results: A phase I study of first-line atezolizumab plus chemotherapy demonstrated efficacy regardless of PD-L1 status and an acceptable safety profile in multiple tumor types. Accordingly, ongoing phase III trials address potential benefits of platinum-based immunotherapy combinations in comparison to standard platinum-containing regimens in first-line NSCLC and SCLC. If additional bevacizumab might further enhance atezolizumab efficacy by inhibiting vascular Endothelial Growth Factor (VEGF)-related immunosuppression is currently investigated in the IMpower150 trial.

Patients under intensive care for advanced cancers develop symptoms due to cancer progression and, possibly, due to therapy-related sideeffects. These symptoms are often not detected promptly by the treating physician leading to functional impairment and deconditioning of the patient's status with potential implications for the general outcome. Improved symptom control in late-stage cancer under exhaustive therapy regimens was achieved through intensified symptom management. Systematic collection of symptom information by electronic patientreported outcomes (ePROs) in addition to clinical routine provides an attractive basis for intensified symptom management. However, despite new, intriguing results, the proof of a significant benefit (defined as primary outcome measure) under first-line treatment is still limited in oncology trials.

In the palliative setting of lung cancer, routine treatment monitoring includes imaging at certain intervals. However, as approaching imaging assessments clarify the patient's fate, they are often a source for anxiety and concern. Additionally, patients with emerging symptoms often wait until the next routinely scheduled consultation with their treating oncologist. As a consequence, tumor progression without therapeutic hindrance over several weeks may occur and naturally shorten the patient's survival time. Clinical monitoring via self-assessed symptom-based approaches endows several benefits. Remarkably, 75-95% of relapses in lung cancer patients come with symptoms and, thus, a direct PRO measurement might be useful in the detection of an early disease progression. Easily accessible web-based application tools such as CANKADO were developed to report PROs more frequently compared to routine assessment. These tools help to strengthen the connection between patient and treating physician and to reduce patients' anxiety. Of note, even during treatment with toxic chemotherapy, most patients are willing and able to self-report via the web. Physicians appreciate PROs and trust in patient-reported information. In line with this, several promising studies confirmed a benefit from proactive, web-based monitoring programs. If symptoms occurred or worsened, the respective physician was informed earlier what resulted n improved OS, quality of life (QoL) and also in economic advantages due to less unnecessary routine check-ups. So far, these studies were performed on heterogeneous patient populations during chemotherapy. The current study is aimed to test the benefit of a web-based application tool in NSCLC, SCLC and TNBC patients during the recently approved first-line treatment strategy with atezolizumab in combination with chemotherapy.

Eligibility criteria: Inclusion criteria

1. Histologically or cytologically confirmed stage IV non-squamous NSCLC or histologically or cytologically confirmed extensive-stage SCLC or histologically or cytologically confirmed advanced (locally advanced and inoperable or metastatic), PD-L1 IC-positive TNBC, respectively
2. Indication and decision for approved therapy with

   1. atezolizumab and bevacizumab in combination with carboplatin and paclitaxel induction followed by atezolizumab/bevacizumab maintenance therapy in accordance with the current German SmPC of atezolizumab for first-line treatment of stage IV non-squamous NSCLC
   2. atezolizumab in combination with carboplatin and nab-paclitaxel induction followed by atezolizumab maintenance therapy in accordance to the current German SmPC of atezolizumab for first-line treatment of stage IV non-squamous NSCLC
   3. atezolizumab in combination with carboplatin and etoposide induction followed by atezolizumab maintenance therapy in accordance to the current German SmPC of atezolizumab for first-line treatment of extensive-stage SCLC
   4. atezolizumab in combination with nab-paclitaxel in accordance to the current German SmPC of atezolizumab for treatment of advanced, PD-L1 IC-positive TNBC
3. Aged ≥ 18 years
4. ECOG 0-2
5. In possession of a web-connected, frequently used, electronic device (smartphone, tablet, PC)
6. Willingness and ability to participate at the paper-based or digital questionnaire project and to participate at an initial training and to regularly use the web-based application tool CANKADO
7. Fluent in written and spoken German
8. Written (signed and dated) informed consent

Exclusion Criteria:

1. Prior treatment for stage IV non-squamous NSCLC (prior TKI therapy is allowed for EGFR mutant or ALK-positive NSCLC) or prior systemic treatment for extensive-stage SCLC or prior systemic chemotherapy for advanced TNBC
2. History of severe (or known) hypersensitivity to chimeric or humanized antibodies or fusion proteins or any component of atezolizumab formulation
3. Pregnant or breast-feeding women

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 72 months
Secondary outcomes:
measure: Best response
timeFrame: 72 months
measure: Overall response rate (ORR)
timeFrame: 72 months
measure: Disease control rate (DCR)
timeFrame: 72 months
measure: Progression Free Survival (PFS)
timeFrame: 72 months
measure: Change from baseline in the global health scale score
timeFrame: 72 months
measure: Change from baseline in the functional/symptom scores
timeFrame: 72 months
measure: Time to deterioration in global health scale score
timeFrame: 72 months
measure: Time to deterioration in functional/symptom scores
timeFrame: 72 months
measure: Alerts
timeFrame: 72 months
measure: Sensitivity of alerts
timeFrame: 72 months
measure: Specifity of alerts
timeFrame: 72 months
measure: Positive predictive value of alerts
timeFrame: 72 months
measure: Negative predictive value of alerts
timeFrame: 72 months
measure: Progression-detection rate
timeFrame: 72 months
measure: Patient compliance
timeFrame: 72 months
measure: Safety and tolerability
timeFrame: 72 months
measure: Treatment duration of first-line atezolizumab
timeFrame: 72 months
measure: Relative dose intensity of first-line atezolizumab
timeFrame: 72 months
measure: Treatment duration of each combined first-line antineoplastic therapy substance
timeFrame: 72 months
measure: Relative dose intensity of each combined first-line antineoplastic therapy substance
timeFrame: 72 months
measure: Treatment duration of combined first-line bevacizumab
timeFrame: 72 months
measure: Treatment modifications of first-line atezolizumab and all combined antineoplastic substances
timeFrame: 72 months
measure: Subsequent antineoplastic therapy lines
timeFrame: 72 months
measure: Subscale scores and single item responses
timeFrame: 72 months
Other outcomes:
Locations:
city: Ahaus
country: Germany
facility: Onkologische Praxis im St. Marien-Krankenhaus
city: Amberg
country: Germany
facility: Gesundheitszentrum St. Marien
city: Arnsberg
country: Germany
facility: Klinikum Arnsberg, Karolinen Hospital
city: Aschaffenburg
country: Germany
facility: MVZ am Klinikum Aschaffenburg
city: Augsburg
country: Germany
facility: Klinikum Augsburg, II. Medizinische Klinik
city: Augsburg
country: Germany
facility: Gemeinschaftspraxis Dr. Heinrich, Prof. Dr. Bangerter
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth GmbH
city: Bergisch Gladbach
country: Germany
facility: Facharztpraxis am VPH Bensberg, Onkologie und Hämatologie
city: Berlin
country: Germany
facility: Onkologisches Versorgungszentrum Friedrichshain
city: Bonn
country: Germany
facility: Praxiskooperation Bonn-Euskirchen
city: Bovenden
country: Germany
facility: Ev. Krankenhaus Göttingen-Weende gGmbH, Pneumologie, Beatmungsmedizin/Schlaflabor
city: Bremen
country: Germany
facility: Hämato- Onkologische Praxis im Medicum
city: Bremen
country: Germany
facility: Klinikum Bremen-Ost, Pneumologie, Beatmungsmedizin
city: Celle
country: Germany
facility: MVZ am Allgemeinen Krankenhaus
city: Dessau
country: Germany
facility: MVZ des Städtischen Klinikums Dessau GmbH
city: Donauwörth
country: Germany
facility: Onkologiezentrum Donauwörth
city: Dortmund
country: Germany
facility: Klinikum Dortmund, Pneumologie, Infektiologie, internistische Intensivmedizin
city: Dresden
country: Germany
facility: Onkologische Gemeinschaftspraxis
city: Duisburg
country: Germany
facility: Sana Kliniken Duisburg GmbH
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
city: Frankfurt (Oder)
country: Germany
facility: Berufsausübungsgemeinschaft am Klinikum
city: Frankfurt a.M.
country: Germany
facility: Centrum für Hämatologie und Onkologie Bethanien
city: Frankfurt a.M.
country: Germany
facility: Klinikum Frankfurt Höchst Innere Medizin 3
city: Frechen
country: Germany
facility: Praxis Internistischer Onkologie und Hämatologie (PIOH)
city: Freiburg im Breisgau
country: Germany
facility: Praxis für interdisziplinäre Onkologie & Hämatologie
city: Freital
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Garbsen
country: Germany
facility: Gemeinschaftspraxis Panagiotou/Minaei (GbR)
city: Georgsmarienhütte
country: Germany
facility: MVZ II der Niels Stensen Kliniken, Onkologie u. Hämatologie
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen, Medizinische Klinik V, Internistische Onkologie und Palliativmedizin
city: Goslar
country: Germany
facility: Überörtliche Berufsausübungsgemeinschaft
city: Göttingen
country: Germany
facility: OSP Göttingen, Dres. Meyer / Ammon / Metz
city: Halle (Saale)
country: Germany
facility: Krankenhaus Martha-Maria Halle-Döla
city: Hamburg
country: Germany
facility: Elbpneumologie im Struenseehaus
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm gGmbH
city: Hannover
country: Germany
facility: MediProjekt GbR
city: Hannover
country: Germany
facility: DIAKOVERE Henriettenstift
city: Heidenheim
country: Germany
facility: Onkologische Schwerpunktpraxis Dr. med. Volker Petersen
city: Heide
country: Germany
facility: Westküstenkliniken Brunsbüttel und Heide, Medizinische Klinik I, Innere Medizin, Hämatologie, Onkologie
city: Herdecke
country: Germany
facility: Gemeinschaftskrankenhaus Herdecke
city: Hildburghausen
country: Germany
facility: Frauenarztpraxis Dr. Lorenz
city: Hildesheim
country: Germany
facility: Praxisgemeinschaft Gynäkologische Onkologie & Spezielle Operative, Gynäkologie
city: Hildesheim
country: Germany
facility: St. Bernward Krankenhaus, Hämatologie & Internistische Onkologie
city: Hildesheim
country: Germany
facility: Onkologische Praxis
city: Homburg (Saar)
country: Germany
facility: Universitätsklinikum des Saarlandes
city: Ilsede
country: Germany
facility: Gynäko-Onkologische Praxis
city: Karlsruhe
country: Germany
facility: St. Vincentius-Kliniken gAG, Gynäkologie und Geburtshilfe
city: Kassel
country: Germany
facility: Hämato-Onkologisches Zentrum Kassel
city: Krefeld
country: Germany
facility: Zentrum für ambulante gynäkologische Onkologie - ZAGO
city: Kronach
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Köthen
country: Germany
facility: Internisten am Markt
city: Landshut
country: Germany
facility: ÜBAG - MVZ Dr. Vehling-Kaiser GmbH Landshut
city: Leipzig
country: Germany
facility: POIS - Leipzig GbR Geßner u. Geßner
city: Lörrach
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Löwenstein
country: Germany
facility: Klinik Löwenstein
city: Marburg
country: Germany
facility: Universitätsklinikum Gießen und Marburg
city: Mayen
country: Germany
facility: Onkologische Gemeinschaftspraxis
city: Mülheim
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und internistische Onkologie
city: München
country: Germany
facility: Hämato-Onkologische Überörtliche Gemeinschaftspraxis
city: Münnerstadt
country: Germany
facility: Thoraxzentrum Bezirk Unterfranken
city: Naunhof
country: Germany
facility: Praxis Dr. med. Jens Uhlig
city: Neuss
country: Germany
facility: MVZ für Onkologie und Hämatologie im Rhein-Kreis Neuss
city: Neustadt Am Rübenberge
country: Germany
facility: MVZ Onko Medical GmbH Neustadt, Innere Med./Hämatologie-Onkologie
city: Nordhorn
country: Germany
facility: Hämatologisch-Onkologische Gemeinschaftspraxis
city: Nürtingen
country: Germany
facility: medius KLINIK NÜRTINGEN
city: Offenburg
country: Germany
facility: Onkologie Offenburg, Ambulantes Therapiezentrum für Hämatologie und Onkologie
city: Oldenburg
country: Germany
facility: Onkologische Praxis Oldenburg
city: Oldenburg
country: Germany
facility: Pius-Hospital Oldenburg Universitätsklinik f. Innere Medizin Hämatologie und Onkologie
city: Plauen
country: Germany
facility: Praxis Dagmar Guth
city: Querfurt
country: Germany
facility: Carl-von-Basedow-Klinikum, Medizinischen Klinik III, Pneumologie
city: Ratingen
country: Germany
facility: Praxis für Hämatologie und internistische Onkologie
city: Recklinghausen
country: Germany
facility: Praxis und Tagesklinik für Onkologie und Hämatologie
city: Remscheid
country: Germany
facility: Onkologische Praxis Remscheid
city: Remscheid
country: Germany
facility: Praxis und Tagesklinik für Onkologie und Hämatologie
city: Riesa
country: Germany
facility: Elblandkliniken Stiftung & Co. KG, Elblandklinikum Riesa
city: Rostock
country: Germany
facility: Klinikum Südstadt Rostock, Innere Medizin III
city: Rostock
country: Germany
facility: Zentrum für Urologie und Onkologie
city: Scheibenberg
country: Germany
facility: Praxis Dipl.-Med. René Schubert
city: Schwäbisch Hall
country: Germany
facility: Diakonie-Klinikum Schwäbisch Hall, Frauenklinik
city: Siegburg
country: Germany
facility: ZAHO Siegburg
city: Soest
country: Germany
facility: MVZ Kloster Paradiese GbR
city: Stolberg
country: Germany
facility: Hämatologie - Onkologie - Stolberg
city: Stralsund
country: Germany
facility: g.SUND Gynäkologie Kompetenzzentrum Stralsund
city: Stuttgart
country: Germany
facility: Vinzenz von Paul Kliniken
city: Troisdorf
country: Germany
facility: Praxisnetzwerk Hämatologie / internistische Onkologie
city: Völklingen
country: Germany
facility: SHG Kliniken Völklingen, Innere Medizin, Pneumologie, Thorakale Onkologie, Palliativmedizin
city: Weiden
country: Germany
facility: MVZ Weiden GmbH
city: Westerstede
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie
city: Wilhelmshaven
country: Germany
facility: Praxisgemeinschaft für Onkologie und Urologie
city: Witten
country: Germany
facility: GIM - Gemeinschaftspraxis Innere Medizin
city: Würselen
country: Germany
facility: MVZ West GmbH Würselen Hämatologie-Onkologie
city: Zittau
country: Germany
facility: Praxis und Tagesklinik für Hämatologie/Onkologie
Study officials:
affiliation: MVZ am Klinikum Aschaffenburg
name: Manfred Welslau, Dr.
role: PRINCIPAL_INVESTIGATOR
References: