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SNCTP000003922 | NCT04245514 | BASEC2019-02378

SAKK 16/18: Strahlentherapie zur Verstärkung des Effekts einer prä-operativen (vor der Tumor-Operation) Immuntherapie bei Patienten mit lokal fortgeschrittenem nicht-kleinzelligem Bronchuskarzinom (NSCLC). Eine Phase-II-Studie, welche an mehreren Spitälern durchgeführt wird.

Data source: BASEC (Imported from 08.11.2024), WHO (Imported from 07.11.2024)
Changed: Sep 4, 2024, 6:34 AM
Disease category: Lung Cancer

Brief description of trial (Data source: BASEC)

Wir wollen mit dieser Studie eine neue Therapieoption bei Patienten mit lokal fortgeschrittenem nicht-kleinzelligem Lungenkrebs (NSCLC) prüfen. Die Frage ist, ob eine zusätzliche Tumorbestrahlung die Wirkung einer Immuntherapie vor der Tumoroperation verbessern kann. Die Teilnehmenden dieser Studie erhalten vor der Tumoroperation folgende Therapien: zuerst Chemotherapie, dann eine Immuntherapie mit gleichzeitiger Strahlentherapie. Die Strahlentherapie erfolgt nach einem von drei unterschiedlichen Protokollen (= Vorgehensweisen) und die Studie untersucht zusätzlich, ob sich die 3 Bestrahlungsprotokolle in ihrer Wirkung unterscheiden

Health conditions investigated(Data source: BASEC)

Lokal fortgeschrittener nicht-kleinzelliger Lungenkrebs

Health conditions (Data source: WHO)

Non-small Cell Lung Cancer;NSCLC

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Die Teilnehmenden werden unter anderem mit dem Medikament Durvalumab behandelt. Diese Immuntherapie ist in der Schweiz zur Behandlung von Lungenkrebs zugelassen. Die Strahlentherapie wird beim Lungenkrebs in verschiedenen Stadien der Erkrankung als Teil einer Standardtherapie eingesetzt. In dieser Studie erfolgt die Strahlentherapie nach 3 unterschiedlichen Bestrahlungsprotokollen. Die Zuteilung der Patientinnen und Patienten in die Bestrahlungsgruppen (je 30 pro Gruppe) wird ausgelost. Die Dauer der Studientherapie beträgt für eine teilnehmende Person in der Regel 16-18 Monate. Danach werden die Studienteilnehmer für die Dauer von weiteren 5 Jahren regelmässig nachkontrolliert.
Die Studie besteht aus drei Phasen: Voruntersuchung, Behandlung und Nachbeobachtung.
In der Phase der Voruntersuchungen werden zahlreiche Untersuchungen durchgeführt, um Ihren Gesundheitszustand und Ihre Eignung für die Studie abzuklären.
Die Behandlung selbst gliedert sich in vier Phasen:
1. Chemotherapie mit Cisplatin und Docetaxel während 9 Wochen. Die Medikamente werden intravenös als Infusion verabreicht.
2. Immuntherapie und Strahlentherapie: Sie erhalten eine Infusion mit dem Medikament Durvalumab. Am gleichen Tag beginnt die Strahlentherapie, die entweder eine oder vier Wochen dauert.
3. Operation mit Entfernung des Tumors
4. Adjuvante (ergänzende) Immuntherapie, die innerhalb von sechs Wochen nach der Operation beginnt. Sie erhalten ein Jahr lang alle vier Wochen eine Infusion mit dem Medikament Durvalumab.
In der Phase der Nachbeobachtung erfolgen regelmässige Nachkontrollen: in den ersten zwei Jahren alle drei Monate, in den nächsten drei Jahren alle sechs Monate.

Interventions (Data source: WHO)

Drug: Durvalumab;Radiation: Radiotherapy

Criteria for participation in trial (Data source: BASEC)

An der Studie können Personen im Alter von 18-75 Jahren teilnehmen, die an einem NSCLC im Stadium T1-4 N2 M0 leiden (Stadium III N2). Das bedeutet, dass der Tumor bereits Ableger in den Lymphknoten im Brustkorb hat, dass aber in anderen Organen keine Metastasen (Tumor-Ableger) vorliegen. Der Tumor in der Lunge muss so beschaffen sein, dass er operativ entfernt werden kann

Exclusion criteria (Data source: BASEC)

Personen, die Autoimmunerkrankungen oder chronische Infektionen haben oder eine Dauertherapie mit Steroiden benötigen können nicht teilnehmen. Auch Patienten, die aufgrund von Zusatzerkrankungen nicht operiert werden können oder sich nicht einer Platin-basierten Chemotherapie unterziehen können, müssen von dieser Studie ausgeschlossen werden.

Inclusion/Exclusion Criteria (Data source: WHO)

Gender: All
Maximum age: 75 Years
Minimum age: 18 Years
Inclusion Criteria:

- Written informed consent according to ICH-GCP regulations before registration and
prior to any trial specific procedures.

- Histologically (cytology is accepted if histology is not possible) confirmed NSCLC
(adeno-, squamous-, large cell carcinoma, or NSCLC not otherwise specified (NOS))
irrespective of genomic aberrations or PD-L1 expression status.

- Tumor stage T1-4>7 N2 M0 (i.e. T1-3 N2 or T4 N2 but T4 only allowed if due to size >
7cm, not allowed if due to invasion or nodule in different ipsilateral lobe),
according to the TNM classification, 8th edition, December 2016 (see Appendix 2).
Mediastinal lymph node staging has to follow the process chart.

- Tumor is considered resectable based on a multidisciplinary tumor board decision
made before neoadjuvant treatment. Resectable is when a complete resection can be
achieved according to Rami-Porta

- Patients with a prior malignancy (except NSCLC) and treated with curative intention
are eligible if all treatment of that malignancy was completed at least 2 years
before registration and the patient has no evidence of disease at registration. Less
than 2 years is acceptable for malignancies with low risk of recurrence and/or no
late recurrence, after consultation with CI.

- Measurable disease per RECIST v1.1 criteria by PET/CT with contrast enhanced
CT-scan.

- Tumor tissue is available for the mandatory translational research (formalin-fixed;
preferably histology, cytology allowed if histology is not possible)

- Age 18-75 years at time of registration

- WHO performance status 0-1

- Adequate bone marrow function: absolute neutrophil count = 1.5 x 109/L, platelet
count = 100 x 109/L, hemoglobin = 90 g/L (transfusion allowed)

- Adequate hepatic function: total bilirubin = 1.5 x ULN (except for patients with
Gilbert's disease = 3.0 x ULN), AST and ALT = 1.5 x ULN, AP = 2.5 x ULN.

- Adequate renal function: calculated creatinine clearance = 60 mL/min, according to
the formula of Cockcroft-Gault

- Appropriate lung function based on the ESTS guidelines:

- For pneumonectomy: FEV1 and DLCO =80%. If one of both <80%, an exercise test
peak VO2 >75% or 20ml/kg/min is needed

- For resection less than pneumonectomy (resection up to the calculated extent):
exercise test peak VO2 =35% or =10ml/kg/min, with predicted postoperative FEV1
and DLCO = 30%.

- NB: if Spiroergometry would be needed according to ESTS guidelines but is not
possible in due time due to patient factors or the center's resources
alternative assessment methods of fitness for resection can be used (e.g. Stair
climbing test, V/P scan)

- Adequate cardiac function according to investigator's decision based on evaluation
of risk according to NYHA classification

- Women of childbearing potential must use highly effective contraception, are not
pregnant or lactating and agree not to become pregnant during trial treatment and
until 90 days after the last dose of investigational drug. A negative pregnancy test
performed within 7 days before registration is required for all women of
childbearing potential.

- Men agree not to donate sperm or to father a child during trial treatment and until
90 days after the last dose of investigational drug.

Exclusion criteria:

- Presence of any distant metastasis or N3 disease. Brain metastases have to be
excluded by CT or MRI.

- Sulcus superior tumors (Pancoast tumors) or T4 for any other reason than size >7cm.

- Any previous treatment for NSCLC

- Any previous treatment with immune checkpoint inhibitors, including durvalumab

- Previous radiotherapy to the chest (with the exception of tangential breast
irradiation with minimal dose to lung and mediastinum, and superficial orthovoltage
or electron irradiation of localized skin lesions)

- Concomitant or recent (within 30 days of registration) treatment with any other
experimental drug and/or enrollment in another clinical trial.

- Concomitant use of other anti-cancer drugs or radiotherapy.

- Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or
IV) unstable angina pectoris, history of myocardial infarction within the last three
months, serious arrhythmias requiring medication (with exception of atrial
fibrillation or paroxysmal supraventricular tachycardia), uncontrolled hypertension.

- Preexisting peripheral neuropathy (> Grade 1)

- Body weight less than 30 kg

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment.

- Known history of allogeneic organ transplant

- Active autoimmune disease or a syndrome requiring systemic treatment within the past
3 months or a documented history of clinically severe autoimmune disease.
Exceptions: vitiligo, resolved childhood asthma/atopy, hypothyroidism stable on
hormone replacement, Sj?gren's syndrome

- Active or prior documented inflammatory bowel disease (e.g. Crohn's disease,
ulcerative colitis)

- Concomitant or prior use of immunosuppressive medication within 28 days before
registration, with the exceptions of intranasal and inhaled corticosteroids, or
systemic corticosteroids which must not exceed 10 mg/day of prednisone or a dose
equivalent corticosteroid, and the premedication for chemotherapy

- Any concomitant drugs contraindicated for use with the trial drugs according to the
approved product information.

- Known hypersensitivity to trial drugs (cisplatin and docetaxel, durvalumab) or to
any excipient

- Any other serious underlying medical, psychiatric, psychological, familial or
geographical condition, which in the judgment of the investigator may interfere with
the planned staging, treatment and follow-up, affect patient compliance or place the
patient at high risk from treatment-related complications.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/ct2/show/NCT04245514

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT04245514
Further information on trial

Recruitment status

Recruiting

Academic title (Data source: WHO)

Immune-modulatory Radiotherapy to Enhance the Effects of Neoadjuvant PD-L1 Blockade After Neoadjuvant Chemotherapy in Patients With Resectable Stage III(N2) Non-small Cell Lung Cancer (NSCLC): A Multicenter Phase II Trial

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Event-free survival (EFS) at 12 months

Secundary end point (Data source: WHO)

Event-free survival (EFS);Recurrence-free survival (RFS) after R0 resection;Overall survival (OS);Objective response (OR) after neoadjuvant chemotherapy;OR after neoadjuvant immuno-radiotherapy;Pathological Complete Response (pCR);Local Major pathological response (MPR);Overall Major pathological response (oMPR);Nodal down-staging to < ypN2;Complete resection

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Aarau, Baden, Basel, Bellinzona, Bern, Brugg, Chur, Freiburg, Geneva, Locarno, Lugano, Mendrisio, Payerne, Riaz, St. Gallen, Tafers, Thun, Winterthur, Zurich

Countries (Data source: WHO)

Germany, Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

SAKK, Dr. Bernhard Scheibe
+41 31 389 91 91
trials@sakk.ch

Contact for general information (Data source: WHO)

Sacha Rothschild, MD;Bernhard Scheibe, PhD
Universit?tsspital Basel
+41 31 389 91 91
trials@sakk.ch

Contact for scientific information (Data source: WHO)

Sacha Rothschild, MD;Bernhard Scheibe, PhD
Universit?tsspital Basel
+41 31 389 91 91
trials@sakk.ch

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Ethikkommission Ostschweiz (EKOS)

Date of authorisation by the ethics committee

12.03.2020

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2019-02378

Secondary ID (Data source: WHO)

SAKK 16/18
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