Öffentliches Studienregister des CCC-München

Studie ImmunoCobiVem

Studie Studiendesign Status Ein-/Auschlusskriterien Therapie Teilnehmer Dokumente Berechtigungen Tumorboards

Studie
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Studienakronym
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ImmunoCobiVem
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Vollständiger Titel
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Eine multizentrische, offene, randomisierte, kontrollierte Phase-II-Studie zur Bewertung der Wirksamkeit und Sicherheit eines Sequenzierungsplans von Cobimetinib plus Vemurafenib, gefolgt von einer Immuntherapie mit einem Anti-PD-L1-Antikörper Atezolizumab zur Behandlung von Patienten mit nicht resezierbarem oder metastasiertem BRAF V600-Mutantenmelanom

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Beschreibung
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7. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of Progression by imaging for at least 4 weeks prior to the first dose of trial Treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 3 weeks prior to trial treatment.
8. History of leptomeningeal metastases
9. History or current evidence of central serous retinopathy (CSR) or retinal vein
occlusion (RVO) or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes).
10. History of retinal degenerative disease.
11. History of allogenic bone marrow transplantation or organ transplantation.
12. History of Gilbert’s syndrome
13. Impaired cardiovascular function or clinically significant cardiovascular diseases, including any of the following:
History of acute coronary syndromes (including myocardial infarction,unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) < 6 months prior to screening.
Symptomatic chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality < 6 months prior to screening except atrial fibrillation and paroxysmal supraventricular tachycardia.
History of congenital long QT syndrome or mean (average of triplicate measurements) QTc measured using Fridericia’s method ≥ 450msec at baseline or uncorrectable abnormalities in serum electrolytes (sodium, potassium, calcium, magnesium, phosphorus).
14. Uncontrolled arterial hypertension despite medical treatment.
15. Patients who have neuromuscular disorders which are associated with elevated CK (e. g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
16. Impairment of gastrointestinal function or gastrointestinal disease (e.g.ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome,small bowel resection).
17. Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
Note: Subjects with vitiligo or controlled asthma/atopy would be an exception to this rule.
Note: Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study.
Note: Subjects with hypothyroidism stable on hormone replacement or Sjorgen’s Syndrome will not be excluded from the study.
18. Evidence of interstitial lung disease or active, non-infectious pneumonitis.
19. Active infection requiring systemic therapy.
20. Pregnancy or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or Screening visit through 120 days after the last dose of trial treatment.
21. The patient is known to be positive for Human Immunodeficiency Virus (HIV)(HIV 1/2 antibodies)
22. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
23. Known hypersensitivity reaction to any of the components of study treatment.
24. Medical, psychiatric, cognitive or other conditions, including known alcohol or drug abuse that would not permit the subject to complete the study or sign informed consent.
25. Patients taking non-topical medication known to be a strong inhibitor of CYP3A4. However patients who either discontinue their treatment or switch to another medication at least three days prior to registration / randomization are eligible.
26. Legal incapacity or limited legal capacity
This is a prospective, open, multicenter, randomized phase II study in patients with unresectable or metastatic BRAFV600 mutant melanoma. In this study the scheduling of the treatment with a combined BRAF/MEK inhibition and the treatment with an anti-PD-L1 antibody will be assessed.

After a 3 months run-in period with vemurafenib and cobimetinib, all patients who did not show disease progression or treatment interruption for more than 28 days during run-in phase will be randomized in a 1:1 Ratio either to proceed vemurafenib and cobimetinib until disease progression and subsequently cross-over to atezolizumab Treatment until disease progression (Arm A)or to receive the anti-PD-L1 antibody atezolizumab until disease progression and subsequently cross-back to vemurafenib and cobimetinib until disease progression (Arm B).
Patients will be stratified according to serum LDH (elevated vs. within normal limits at enrollment), metastatic stage (M1a/b vs. M1c), previous therapy (yes/no).

In a translational research program tumor tissue, blood plasma and peripheral blood mononuclear cell will be analyzed to evaluate the biologic effects of treatment sequence on the molecular profile and biomarker expression in tissue and plasma.

Dies ist eine prospektive, offene, multizentrische, randomisierte Phase-II-Studie bei Patienten mit nicht resezierbarem oder metastasiertem mutiertem BRAFV600-Melanom. In dieser Studie wird die Planung der Behandlung mit einer kombinierten BRAF / MEK-Hemmung und die Behandlung mit einem Anti-PD-L1-Antikörper bewertet.

Nach einer Einlaufzeit von 3 Monaten mit Vemurafenib und Cobimetinib werden alle Patienten, die während der Einlaufphase länger als 28 Tage kein Fortschreiten der Krankheit oder keine Unterbrechung der Behandlung zeigten, im Verhältnis 1: 1 randomisiert, um entweder mit Vemurafenib und Cobimetinib fortzufahren Fortschreiten der Erkrankung und anschließende Umstellung auf Atezolizumab Behandlung bis zum Fortschreiten der Erkrankung (Arm A) oder Erhalt des Anti-PD-L1-Antikörpers Atezolizumab bis zum Fortschreiten der Erkrankung und anschließende Rückübertragung auf Vemurafenib und Cobimetinib bis zum Fortschreiten der Erkrankung (Arm B).
Die Patienten werden nach Serum-LDH (erhöht vs. innerhalb der normalen Grenzen bei der Aufnahme), metastasiertem Stadium (M1a / b vs. M1c) und vorheriger Therapie (ja / nein) geschichtet.

In einem translationalen Forschungsprogramm werden Tumorgewebe, Blutplasma und mononukleäre Zellen des peripheren Blutes analysiert, um die biologischen Auswirkungen der Behandlungssequenz auf das molekulare Profil und die Biomarkerexpression in Gewebe und Plasma zu bewerten.

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EudraCT-Nr.
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NCT-Nr.
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Zuständige Einrichtung
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Klinik f. Dermatologie/Allerg., Telefon: 089440056010
Krankheitsentitäten
Klassifikation Code Beschreibung
- Krebserkrankungen der Haut
Studiendesign
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Studientyp
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Interventionsstudie
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Verblindungstyp
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Offen
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Studienphase
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II
Status
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Status
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Studie beendet
Voten
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Ethikkommission - Votum
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Unbekannt
Initiierung & Abschluß
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Abschlussdatum (Plan / Ist)
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2024-06-30 / 2020-06-16
Teilnehmer
Funktion Vorname Nachname Einrichtung
World Hauptprüfer Carola Berking Keine Organisationseinheit angegeben Magnifier
World Hauptprüfer LUCIE HEINZERLING Keine Organisationseinheit angegeben Magnifier