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JOURNAL ONKOLOGIE – STUDIE

Advancing Brigatinib Properties in ALK+ NSCLC Patients by Deep Phenotyping

Rekrutierend

NCT-Nummer:
NCT04318938

Studienbeginn:
März 2020

Letztes Update:
12.11.2020

Wirkstoff:
Brigatinib, Tyrosine kinase inhibitor

Indikation (Clinical Trials):
Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

Collaborator:
-

Studienleiter

Salah-Eddin Al-Batran, Prof.
Study Director
Institut für Klinische Krebsforschung IKF GmbH

Kontakt

Michael Thomas, Prof.
Kontakt:
Phone: +49 6221 396
Phone (ext.): 1301
E-Mail: Michael.Thomas@med.uni-heidelberg.de
» Kontaktdaten anzeigen
Regina Eickhoff, Dr.
Kontakt:
Phone: +49 69 7601
Phone (ext.): 4165
E-Mail: eickhoff.regina@ikf-khnw.de
» Kontaktdaten anzeigen

Studienlocations
(3 von 18)

Brustkrebszentrum am Westdeutschen Tumorzentrum - Universitätsmedizin Essen
Hufelandstraße 55
45147 Essen
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Marcel Wiesweg, Dr.
E-Mail: marcel.wiesweg@uk-essen.de
» Ansprechpartner anzeigen
Interdisziplinäres Brustzentrum am Klinikum Esslingen
Hirschlandstraße 97
73730 Esslingen am Neckar
(Baden-Württemberg)
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Martin Faehling, Dr.
E-Mail: m.faehling@klinikum-esslingen.de
» Ansprechpartner anzeigen
Niels-Stensen-Kliniken Georgsmarienhütte
49124 Georgsmarienhütte
(Niedersachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Petra Hoffknecht, Dr.
E-Mail: Petra.Hoffknecht@niels-stensen-kliniken.de
» Ansprechpartner anzeigen
Klinik Schillerhöhe Gerlingen
Gerlingen
(Baden-Württemberg)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Evelin Anne-Marie Sandner, Dr. Dr.
E-Mail: evelin.sandner@klinik-schillerhoehe.de
» Ansprechpartner anzeigen
Thoraxklinik am Universitätsklinikum Heidelberg
69126 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Michael Thomas, Prof. Dr.
Phone: +49 6221 396
Phone (ext.): 1301
E-Mail: Michael.Thomas@med.uni-heidelberg.de

Petros Christopoulos, Dr. med.
Phone: +49 6221 396
Phone (ext.): 8041
» Ansprechpartner anzeigen
Gynäkologisches Tumorzentrum am Universitätsklinikum Leipzig
4103 Leipzig
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Hubert Wirtz, Prof. Dr.
E-Mail: Hubert.wirtz@medizin.uni-leipzig.de
» Ansprechpartner anzeigen
Darmkrebszentrum der Universitätsmedizin Mainz
Langenbeckstraße 1
55131 Mainz
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Jürgen Alt, Dr.
E-Mail: juergen.alt@unimedizin-mainz.de
» Ansprechpartner anzeigen
Interdisziplinäres Brustzentrum Klinikum Nürnberg
Prof.-Ernst-Nathan-Straße 1
90419 Nürnberg
(Bayern)
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Wolfgang Brückl, Prof. Dr.
E-Mail: wolfgang.brueckl@klinikum-nuernberg.de
» Ansprechpartner anzeigen
Pankreaskarzinomzentrum Universitätsklinikum Regensburg
Franz-Josef-Strauß-Allee 11
93053 Regensburg
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Maximilian Malfertheiner, Dr
E-Mail: maximilian.malfertheiner@ukr.de
» Ansprechpartner anzeigen
Leberkrebszentrum Universitätsklinikum Ulm
Albert-Einstein-Allee 23
89081 Ulm
DeutschlandRekrutierend» Google-Maps
Ansprechpartner:
Gerlinde Schmidtke-Schrezenmeier, Dr.
E-Mail: gerlinde.schmidtke-schrezenmeier@uniklinik-ulm.de
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Detailed Description:

The aim of this study is to compare efficacy of brigatinib and other 2nd-generation ALK

tyrosin kinase inhibitor (TKI) in 1st and 2nd line treatment and to explore resistance

patterns according to treatment and molecular properties of the tumors

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Fully informed written consent and any locally-required authorization (EU Data Privacy

Directive) given by the patient

2. Male or female ≥ 18 years of age NOTE: There are no data that indicate special gender

distribution. Therefore, patients will be enrolled in the study gender-independently.

3. Histologically confirmed locally advanced (stage III) and not suitable for curative

treatment, i.e. R0 operation or definitive chemo-/radiation, or metastatic (stage IV)

ALK+ NSCLC NOTE: Documentation of ALK rearrangement by a positive result of any ALK

assay approved in Germany [i.e. positivity for at least one of the three:

immunohistochemistry (IHC), NGS, fluorescence in situ hybridisation (FISH)] must be

available at baseline. Treatment can already be started based on a local ALK+ test

result, but subsequent central testing of the baseline biopsy for molecular profiling,

incl. determination of ALK variant and TP53 status, should be made possible for all

patients.

4. No prior therapy for metastatic ALK+ NSCLC including therapy with ALK inhibitors.

However, 1 or 2 cycles of chemotherapy as well as cerebral irradiation before

inclusion in the study will be allowed.

5. At least 1 measurable (i.e., target) lesion per RECIST v1.1

6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

7. Have adequate organ function, as determined by:

- Total bilirubin ≤1.5x the upper limit of the normal range (ULN) (< 3x the ULN if

Gilbert's disease is present)

- Estimated glomerular filtration rate ≥30 mL/minute/1.73 m2 (calculated by

Modification of Diet in Renal Disease (MDRD) or any other validated formula, see

Appendix 13.4)

- Alanine aminotransferase/aspartate aminotransferase ≤2.5x ULN NOTE: ≤5x ULN is

acceptable if liver metastases are present.

- Serum lipase ≤1.5x ULN

- Platelet count ≥75x 109/L

- Hemoglobin ≥9 g/dL

- Absolute neutrophil count ≥1.5x 109/L

8. Willingness and ability to comply with scheduled visit and study procedures

9. Patient willing to participate in accompanying research program

10. Collection of current biopsy during screening must be feasible NOTE: For each patient

a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block must be available for

biomarker evaluation. Excisional, incisional or core needle biopsies are appropriate,

while fine needle aspirations are insufficient.

11. Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7

days prior to randomization. Women must not be breastfeeding.

12. Female patients who:

- are postmenopausal for at least 1 year before the screening visit, OR

- are surgically sterile, OR

- if they are of childbearing potential, agree to practice highly effective

non-hormonal contraception from the time of signing the informed consent through

at least 4 months after the last dose of study drug, or agree to completely

abstain from heterosexual intercourse.

Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:

- agree to practice effective barrier contraception during the entire study treatment

period and through at least 4 months after the last dose of study drug, OR

- agree to completely abstain from heterosexual intercourse.

Exclusion Criteria:

1. History or presence at baseline of pulmonary interstitial disease, drug-related

pneumonitis, or radiation pneumonitis

2. Uncontrolled hypertension, defined as hypertension treated* with anti-hypertensive

drugs AND blood pressure ≥ 160 mmHg (systolic) or ≥ 100 mmHg (diastolic) in repeated

measurements. Untreated elevated blood pressure is not an exclusion criterion and

should receive adequate anti-hypertensive adjustment.

*Please note: In case of treatment, at least 3 anti-hypertensive drugs should have

been used with the intention to control hypertensive disease

3. Systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors, strong CYP3A

inducers, or moderate CYP3A inducers or treatment with any investigational systemic

anticancer agents, chemotherapy or radiation therapy (except for stereotactic

radiosurgery or stereotactic body radiation therapy) within 14 days of randomization

4. Treatment with antineoplastic monoclonal antibodies within 30 days of randomization

5. Major surgery within 30 days of randomization. Minor surgical procedures, such as

catheter placement or minimally invasive biopsies, are allowed.

6. Current spinal cord compression (symptomatic or asymptomatic) as detected by

radiographic imaging. Patients with leptomeningeal disease without cord compression

are allowed.

7. Significant or uncontrolled cardiovascular disease, defined as to the following:

- If an acute myocardial infarction has ensued in the past 6 months, successful

reperfusion has to be documented and the patient has to be free of symptoms

- New York Heart Association Class III or IV heart failure (i.e. marked limitation

in activity due to symptoms, even during less-than-ordinary activity, e.g.

walking short distances (20-100 m). Comfortable only at rest) within 6 months

prior to randomization

- Any history of clinically significant ventricular arrhythmia, defined as

ventricular tachycardia (VT), ventricular fibrillation (VF), or cardiac arrest

8. Cerebrovascular accident or transient ischemic attack within 6 months prior to first

dose of study drug

9. Malabsorption syndrome or other gastrointestinal illness or condition that could

affect oral absorption of the study drug

10. Active severe or uncontrolled chronic infection, including but not limited to, the

requirement for intravenous antibiotics for longer than 2 weeks

11. History of HIV infection. Testing is not required in the absence of history.

12. Chronic hepatitis B (surface antigen-positive) or chronic active hepatitis C

infection. Testing is not required in the absence of history.

13. Any serious medical condition or psychiatric illness that could, in the investigator's

opinion, potentially compromise patient safety or interfere with the completion of

treatment according to this protocol

14. Known or suspected hypersensitivity to brigatinib or other TKI or their excipients

15. Life-threatening illness unrelated to cancer

16. Involvement in the planning and/or conduct of the study (applies to both Takeda staff

and/or staff of sponsor and study site)

17. Patient who might be dependent on the sponsor, site or the investigator

18. Patient who has been incarcerated or involuntarily institutionalized by court order or

by the authorities [according to national Medicinal Products Act (Arzneimittelgesetz,

AMG)]

19. Patients who are unable to consent because they do not understand the nature,

significance and implications of the clinical trial and therefore cannot form a

rational intention in the light of the facts [according to national AMG]

20. Legal incapacity or limited legal capacity

21. Females who are pregnant or breastfeeding

22. Patients who have symptomatic CNS metastases (parenchymal or leptomeningeal) at

screening or asymptomatic disease requiring an increasing dose of corticosteroids to

control symptoms within 7 days prior to randomization.

NOTE: If a patient has worsening neurological symptoms or signs due to CNS metastasis,

the patient needs to complete local therapy and be neurologically stable (with no

requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7

days prior to randomization.

23. Rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose

malabsorption

Studien-Rationale

Primary outcome:

1. Progression-free survival (PFS) of 1st-line treatment according to RECIST v1.1 (Time Frame - 68 months):
Time from the first dosing date of any study medication to the date of the first objectively documented tumor progression or death due to any cause



Secondary outcome:

1. PFS of 2nd-line treatment according to RECIST v1.1 (Time Frame - 68 months):
Time from the first dosing date of any 2nd-line TKI to the date of the objectively documented tumor progression or death due to any cause

2. TNT 1st line (TNT1, i.e. time-to-next treatment for the 1st line) (Time Frame - 68 months):
Time from begin of 1st-line treatment until begin of 2nd-line treatment

3. TNT 2nd line (TNT2, i.e. time-to-next treatment for the 2nd line (Time Frame - 68 months):
Time from begin of 2nd line until begin of 3rd-line treatment

4. TNT1/2 (time-to-next treatment for the 1st and 2nd line together) (Time Frame - 68 months):
Time from begin of 1st-line treatment until begin of 3rd-line treatment

5. Overall survival (OS) (Time Frame - 68 months):
Time from treatment start in the 1st line to the date of death (due to any cause)

6. Intracranial ORR (iORR) (Time Frame - 68 months):
Percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation, recorded between the date of first dose and the date of the initial objectively documented intracranial tumor progression per RECIST criteria or the date of subsequent therapy or death, whichever occurs first

7. Intracranial DOR (iDOR) according to RECIST v1.1 (Time Frame - 68 months):
Time from documentation of CR or PR according to RECIST v1.1 (whichever is first recorded) until the first date that the intracranial progressive disease (PD) is objectively documented or until death (whichever occurs first

8. Time to intracranial progression (TTiP) (Time Frame - 68 months):
Time from start of 1st-line treatment until the occurrence of a new central nervous system (CNS) lesion or progression of pre-existing CNS lesions

9. Safety (rate of adverse events) (Time Frame - 68 months):
Type, incidence and severity of adverse events (AEs) and serious adverse events (SAEs)graded according to NCI CTCAE v5.0

10. Quality of life (QoL) assessed by SF-12-questionnaire (Time Frame - 68 months):
Patient reported outcome assessed by the validated SF-12-questionnaire

11. Quality of life (QoL) assessed by EORTC-quality of life questionnaire (QLQ)-BN20-questionnaire (Time Frame - 68 months):
Patient reported outcome assessed by the validated EORTC-QLQ-BN20-questionnaire

Studien-Arme

  • Active Comparator: Standard Arm with any available ALK TKI
    st line: Any approved 2nd-generation TKI according to investigator's choice nd line: Any available ALK TKI according to investigator's choice (patients from the standard Arm A can be offered brigatinib in the 2nd line)
  • Experimental: Experimental Arm with Brigatinib
    st line: 90 mg brigatinib once daily p.o. for the first 7 days (lead-in) followed by 180 mg brigatinib once daily p.o. afterwards, starting with day 8 nd line: Any available ALK TKI according to investigator's choice

Geprüfte Regime

  • Brigatinib (Study treatment):
    Treatment with Brigatinib
  • Tyrosine kinase inhibitor (Study treatment):
    Treatment with any TKI

Quelle: ClinicalTrials.gov


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