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

Stage IV Non-small Cell Lung Cancer Clinical Trial

— CHAPLIN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03911219
• Other study ID #: iOM-100392
• Secondary ID: ML41161
• Status: Completed
• Start date: July 10, 2019
• Est. completion date: July 1, 2021

Study information

• Verified date: October 2021
• Source: iOMEDICO AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced (Locally Advanced and Inoperable or Metastatic), PD-L1 IC-positive TNBC
• Extensive-stage Small Cell Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma
• Stage IV Non-small Cell Lung Cancer

Intervention

Other:
• eHealth system support for symptom management via CANKADO
Regular use of eHealth support system CANKADO by the patient: symptom self-reporting triggering alerts to the patient; in addition to standard of care symptom management.

Locations

Country	Name	City	State
Germany	Onkologische Praxis im St. Marien-Krankenhaus	Ahaus
Germany	Gesundheitszentrum St. Marien	Amberg
Germany	Klinikum Arnsberg, Karolinen Hospital	Arnsberg
Germany	MVZ am Klinikum Aschaffenburg	Aschaffenburg
Germany	Gemeinschaftspraxis Dr. Heinrich, Prof. Dr. Bangerter	Augsburg
Germany	Klinikum Augsburg, II. Medizinische Klinik	Augsburg
Germany	Klinikum Bayreuth GmbH	Bayreuth
Germany	Facharztpraxis am VPH Bensberg, Onkologie und Hämatologie	Bergisch Gladbach
Germany	Onkologisches Versorgungszentrum Friedrichshain	Berlin
Germany	Praxiskooperation Bonn-Euskirchen	Bonn
Germany	Ev. Krankenhaus Göttingen-Weende gGmbH, Pneumologie, Beatmungsmedizin/Schlaflabor	Bovenden
Germany	Hämato- Onkologische Praxis im Medicum	Bremen
Germany	Klinikum Bremen-Ost, Pneumologie, Beatmungsmedizin	Bremen
Germany	MVZ am Allgemeinen Krankenhaus	Celle
Germany	MVZ des Städtischen Klinikums Dessau GmbH	Dessau
Germany	Onkologiezentrum Donauwörth	Donauwörth
Germany	Klinikum Dortmund, Pneumologie, Infektiologie, internistische Intensivmedizin	Dortmund
Germany	Onkologische Gemeinschaftspraxis	Dresden
Germany	Sana Kliniken Duisburg GmbH	Duisburg
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Berufsausübungsgemeinschaft am Klinikum	Frankfurt (Oder)
Germany	Centrum für Hämatologie und Onkologie Bethanien	Frankfurt a.M.
Germany	Klinikum Frankfurt Höchst Innere Medizin 3	Frankfurt a.M.
Germany	Praxis Internistischer Onkologie und Hämatologie (PIOH)	Frechen
Germany	Praxis für interdisziplinäre Onkologie & Hämatologie	Freiburg im Breisgau
Germany	Onkologische Schwerpunktpraxis	Freital
Germany	Gemeinschaftspraxis Panagiotou/Minaei (GbR)	Garbsen
Germany	MVZ II der Niels Stensen Kliniken, Onkologie u. Hämatologie	Georgsmarienhütte
Germany	SRH Wald-Klinikum Gera GmbH	Gera
Germany	Universitätsklinikum Gießen, Medizinische Klinik V, Internistische Onkologie und Palliativmedizin	Gießen
Germany	Überörtliche Berufsausübungsgemeinschaft	Goslar
Germany	OSP Göttingen, Dres. Meyer / Ammon / Metz	Göttingen
Germany	Krankenhaus Martha-Maria Halle-Döla	Halle (Saale)
Germany	Elbpneumologie im Struenseehaus	Hamburg
Germany	Evangelisches Krankenhaus Hamm gGmbH	Hamm
Germany	DIAKOVERE Henriettenstift	Hannover
Germany	MediProjekt GbR	Hannover
Germany	Westküstenkliniken Brunsbüttel und Heide, Medizinische Klinik I, Innere Medizin, Hämatologie, Onkologie	Heide
Germany	Onkologische Schwerpunktpraxis Dr. med. Volker Petersen	Heidenheim
Germany	Gemeinschaftskrankenhaus Herdecke	Herdecke
Germany	Frauenarztpraxis Dr. Lorenz	Hildburghausen
Germany	Onkologische Praxis	Hildesheim
Germany	Praxisgemeinschaft Gynäkologische Onkologie & Spezielle Operative, Gynäkologie	Hildesheim
Germany	St. Bernward Krankenhaus, Hämatologie & Internistische Onkologie	Hildesheim
Germany	Universitätsklinikum des Saarlandes	Homburg (Saar)
Germany	Gynäko-Onkologische Praxis	Ilsede
Germany	St. Vincentius-Kliniken gAG, Gynäkologie und Geburtshilfe	Karlsruhe
Germany	Hämato-Onkologisches Zentrum Kassel	Kassel
Germany	Internisten am Markt	Köthen
Germany	Zentrum für ambulante gynäkologische Onkologie - ZAGO	Krefeld
Germany	Onkologische Schwerpunktpraxis	Kronach
Germany	ÜBAG - MVZ Dr. Vehling-Kaiser GmbH Landshut	Landshut
Germany	POIS - Leipzig GbR Geßner u. Geßner	Leipzig
Germany	Onkologische Schwerpunktpraxis	Lörrach
Germany	Klinik Löwenstein	Löwenstein
Germany	Universitätsklinikum Gießen und Marburg	Marburg
Germany	Onkologische Gemeinschaftspraxis	Mayen
Germany	Gemeinschaftspraxis für Hämatologie und internistische Onkologie	Mülheim
Germany	Hämato-Onkologische Überörtliche Gemeinschaftspraxis	München
Germany	Thoraxzentrum Bezirk Unterfranken	Münnerstadt
Germany	Praxis Dr. med. Jens Uhlig	Naunhof
Germany	MVZ für Onkologie und Hämatologie im Rhein-Kreis Neuss	Neuss
Germany	MVZ Onko Medical GmbH Neustadt, Innere Med./Hämatologie-Onkologie	Neustadt Am Rübenberge
Germany	Hämatologisch-Onkologische Gemeinschaftspraxis	Nordhorn
Germany	medius KLINIK NÜRTINGEN	Nürtingen
Germany	Onkologie Offenburg, Ambulantes Therapiezentrum für Hämatologie und Onkologie	Offenburg
Germany	Onkologische Praxis Oldenburg	Oldenburg
Germany	Pius-Hospital Oldenburg Universitätsklinik f. Innere Medizin Hämatologie und Onkologie	Oldenburg
Germany	Praxis Dagmar Guth	Plauen
Germany	Carl-von-Basedow-Klinikum, Medizinischen Klinik III, Pneumologie	Querfurt
Germany	Praxis für Hämatologie und internistische Onkologie	Ratingen
Germany	Praxis und Tagesklinik für Onkologie und Hämatologie	Recklinghausen
Germany	Onkologische Praxis Remscheid	Remscheid
Germany	Praxis und Tagesklinik für Onkologie und Hämatologie	Remscheid
Germany	Elblandkliniken Stiftung & Co. KG, Elblandklinikum Riesa	Riesa
Germany	Klinikum Südstadt Rostock, Innere Medizin III	Rostock
Germany	Zentrum für Urologie und Onkologie	Rostock
Germany	Praxis Dipl.-Med. René Schubert	Scheibenberg
Germany	Diakonie-Klinikum Schwäbisch Hall, Frauenklinik	Schwäbisch Hall
Germany	ZAHO Siegburg	Siegburg
Germany	MVZ Kloster Paradiese GbR	Soest
Germany	Hämatologie - Onkologie - Stolberg	Stolberg
Germany	g.SUND Gynäkologie Kompetenzzentrum Stralsund	Stralsund
Germany	Vinzenz von Paul Kliniken	Stuttgart
Germany	Praxisnetzwerk Hämatologie / internistische Onkologie	Troisdorf
Germany	SHG Kliniken Völklingen, Innere Medizin, Pneumologie, Thorakale Onkologie, Palliativmedizin	Völklingen
Germany	MVZ Weiden GmbH	Weiden
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie	Westerstede
Germany	Praxisgemeinschaft für Onkologie und Urologie	Wilhelmshaven
Germany	GIM - Gemeinschaftspraxis Innere Medizin	Witten
Germany	MVZ West GmbH Würselen Hämatologie-Onkologie	Würselen
Germany	Praxis und Tagesklinik für Hämatologie/Onkologie	Zittau

Sponsors (2)

Lead Sponsor	Collaborator
iOMEDICO AG	Roche Pharma AG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Time from randomization to death from any cause. Patients not experiencing an event (i.e., patients alive at their individual end of study) will be censored with the last date the patient was known to be alive.	72 months
Secondary	Best response	The best documented response (in terms of complete response [CR], partial response [PR], stable disease [SD], or progressive disease [PD]) per patient, as assessed by the treating physician.	72 months
Secondary	Overall response rate (ORR)	The proportion of patients showing a best overall response of CR or PR (as assessed by the treating physician).	72 months
Secondary	Disease control rate (DCR)	The proportion of patients showing a best overall response of CR, PR, or SD (as assessed by the treating physician).	72 months
Secondary	Progression Free Survival (PFS)	The time from randomization to tumor progression or death from any cause, whatever occurs first. Patients being event-free (i.e., alive and progression-free) by the time of analysis or starting a new antineoplastic therapy before progression, will be censored at the date of the last adequate tumor assessment.	72 months
Secondary	Change from baseline in the global health scale score	To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Change from baseline in the global health scale score	72 months
Secondary	Change from baseline in the functional/symptom scores	To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Change from baseline in the functional/symptom scores	72 months
Secondary	Time to deterioration in global health scale score	To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Time to deterioration (TTD) by = 10 points in the global health scale score	72 months
Secondary	Time to deterioration in functional/symptom scores	To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms: Time to deterioration (TTD) by = 10 points in the functional/symptom scores	72 months
Secondary	Alerts	Frequency and total number of eHealth Support system (EHSS) alerts.	72 months
Secondary	Sensitivity of alerts	Ratio of alert-initiated visits that result in detection of tumor progression and/or action-requiring symptom management (as evaluated by the oncologist) and all visits which result in detection of tumor progression and/or action-requiring symptom management.	72 months
Secondary	Specifity of alerts	Ratio of non-alert-initiated visits with neither detected tumor progression nor action-requiring symptom management (as evaluated by the oncologist) and all visits with neither detected tumor progression nor action-requiring symptom management.	72 months
Secondary	Positive predictive value of alerts	Ratio of alert-initiated visits that resulted in detection of tumor progression and/or action-requiring symptom management and all alert-initiated visits.	72 months
Secondary	Negative predictive value of alerts	Ratio of non-alert-initiated visits with no result (i.e., neither detected tumor progression nor action-requiring symptom management) and all non-alert-initiated visits.	72 months
Secondary	Progression-detection rate	The proportion of individuals who test positive for a first tumor progression during atezolizumab therapy in a specific type of tumor assessment (i.e., alert-triggered vs. non-alert-triggered), compared to the total number of first detected progressions during atezolizumab therapy (i.e., progressions detected in all tumor assessments during scheduled as well as unscheduled visits).	72 months
Secondary	Patient compliance	Intensity of use of application tool (defined as number of utilizations per week over the total observation time).	72 months
Secondary	Safety and tolerability	Frequency and severity of (serious) adverse events ((S)AEs) coded by the Medical Dictionary for Regulatory Activities (MedDRA), summarized by Preferred Term and System Organ Class and graded according to CTCAE v5.0.; Frequency and severity of (serious) adverse drug reactions ((S)ADRs) with causal relationship to bevacizumab and/or atezolizumab coded by the MedDRA, summarized by Preferred Term and System Organ Class and graded according to CTCAE v5.0.	72 months
Secondary	Treatment duration of first-line atezolizumab	Treatment duration of first-line atezolizumab (including maintenance therapy)	72 months
Secondary	Relative dose intensity of first-line atezolizumab	Relative dose intensity of first-line atezolizumab (including maintenance therapy)	72 months
Secondary	Treatment duration of each combined first-line antineoplastic therapy substance	Treatment duration of each combined first-line antineoplastic therapy substance	72 months
Secondary	Relative dose intensity of each combined first-line antineoplastic therapy substance	Relative dose intensity of each combined first-line antineoplastic therapy substance	72 months
Secondary	Treatment duration of combined first-line bevacizumab	Treatment duration of combined first-line bevacizumab (including maintenance therapy)	72 months
Secondary	Treatment modifications of first-line atezolizumab and all combined antineoplastic substances	Therapy details and subsequent therapy lines based on Treatment modifications of first-line atezolizumab and all combined antineoplastic substances	72 months
Secondary	Subsequent antineoplastic therapy lines	Therapy details and subsequent antineoplastic therapy lines	72 months
Secondary	Subscale scores and single item responses	To compare patient-reported outcomes (PROs) on quality of life (QoL) of the two study arms Subscale scores and single item responses in Patient Reported Outcomes on QoL in both arms	72 months