Studien für das Tumorboard:
Bonn: Hauttumoren

Diagnosen

Malignes Melanom

Einschlusskriterien

siehe angehängtes Protokoll

Sonstiges

Ausschlusskriterien

Diagnosen

Solide Tumore, Kleinzelliges Bronchialkarzinom (SCLC), Malignes Melanom, Kopf-Hals-Karzinom, Ovarialkarzinome (Eierstockkrebs), Nicht-Kleinzelliges Bronchialkarzinom (NSCLC)

Einschlusskriterien

Main inclusion criteria:

• Pathologically confirmed advanced and/or metastatic solid tumor
• Patients may enter screening procedure before, during, or after the last available indicated standard of care treatment. There is no limitation for prior anti cancer treatments.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• HLA phenotype positive
• Measurable disease and accessible to biopsy
• Adequate pulmonary function per protocol
• Acceptable organ and bone marrow function per protocol
• Acceptable coagulation status per protocol
• Adequate hepatic function per protocol
• Serum creatinine within normal range for age OR creatinine clearance with a recommended estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2
• Patient's tumor must express tumor antigen by qPCR using a fresh tumor biopsy specimen
• Life expectancy more than 3 months
• Confirmed availability of production capacities for IMA203 product
• Patients must have recurrent/progressing and/or refractory solid tumors and must have received or not be eligible for all available indicated standard of care treatment.

Sonstiges

Kontaktpersonen

tobias.holderried@ukb.uni-bonn.de

Ausschlusskriterien

Main exclusion criteria:

• History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within the last 3 years
• Solid tumors with low likelihood of tumor biomarker expression per protocol
• Pregnant or breastfeeding
• Serious autoimmune disease Note: At the discretion of the investigator, these patients may be included if their disease is well controlled without the use of immunosuppressive agents.
• History of cardiac conditions as per protocol
• Prior stem cell transplantation or solid organ transplantation

Diagnosen

Solide Tumore, Kolorektale Karzinome (Darmkrebs), Kleinzelliges Bronchialkarzinom (SCLC), Malignes Melanom, Nicht-Kleinzelliges Bronchialkarzinom (NSCLC)

Einschlusskriterien

•  Histologisch oder zytologisch bestätigte Diagnose eines lokal fortgeschrittenen oder metastasierten soliden Tumors (einschließlich primärer ZNS-Tumore; Stadium IV, American Joint Committee on Cancer v.7), der ein ALK-, ROS1-, NTRK1-, NTRK2- oder NTRK3-Gen-Rearrangement aufweist
• Alle Probanden müssen eine archivierte Gewebeprobe oder eine de novo Gewebeprobe zur Verfügung haben, die vor der Rekrutierung gesammelt wurde. Formalin-fixierte, paraffin-eingebettete (FFPE) Gewebeblöcke von der Erstdiagnose, die genügend Gewebe enthalten, um mindestens 10 (vorzugsweise 15), 5 Mikrometer dicke, ungefärbte Objektträger zu erstellen, werden gesammelt.
• Eine vorherige zytotoxische Chemotherapie bei fortgeschrittener oder metastasierter Erkrankung ist erlaubt. Zum Zeitpunkt des Beginns der Behandlung mit Repotrectinib müssen mindestens 14 Tage oder 5 Halbwertszeiten (je nachdem, was kürzer ist) nach Absetzen der vorherigen zytotoxischen Chemotherapie verstrichen sein (bzw. mindestens 42 Tage bei vorherigen Nitrosoharnstoffen, Mitomycin C und liposomalem Doxorubicin) und alle Nebenwirkungen der vorherigen Behandlungen müssen auf Grad ≤ 1 (CTCAE Version 4.03) abgeklungen sein, mit Ausnahme von Alopezie.
• Eine vorherige Immuntherapie (z. B. Anti-PD-1, Anti-PDL1, Anti-TIM3, Anti-OX40) ist erlaubt (außer in der behandlungsnaiven Expansionskohorte). Zum Zeitpunkt des Beginns der Behandlung mit Repotrectinib müssen mindestens 14 Tage nach Absetzen der vorherigen Immuntherapie verstrichen sein und alle immunbezogenen Nebenwirkungen der vorherigen Behandlungen müssen auf einen Grad ≤ 1 abgeklungen sein.
• [...]

Sonstiges

Kontaktpersonen

juergen.wolf@uk-koeln.de

Ausschlusskriterien

•  Krebs in der Vorgeschichte, außer Plattenepithel- oder Basalzellkarzinom der Haut oder ein vollständig reseziertes In-situ-Karzinom, das innerhalb der letzten 2 Jahre eine Therapie erforderte.
• Klinisch signifikante kardiovaskuläre Erkrankung (entweder aktiv oder innerhalb der letzten 6 Monate vor Studienbeginn): Myokardinfarkt, instabile Angina pectoris, koronare/periphere Arterien-Bypass-Transplantation, symptomatische kongestive Herzinsuffizienz (New York Heart Association Classification Class ≥ II), zerebrovaskulärer Unfall oder transitorische ischämische Attacke, symptomatische Bradykardie, Bedarf an anti-arrhythmischen Medikamenten. Anhaltende Herzrhythmusstörungen von CTCAE-Grad ≥2.
• [...]

Diagnosen

Malignes Melanom

Einschlusskriterien

Inclusion criteria for all subjects

6. ≥ 18 years of at the time of informed consent

7. Written informed consent must be obtained prior to any screening procedures

8. Histologically confirmed, unresectable or metastatic melanoma (stage IIIC or IV)

9. BRAF V600 mutation positive melanoma as assessed locally, or if local BRAF testing is unavailable, at a Novartis designated central reference laboratory

10. Measurable disease per RECIST 1.1.

11. Treatment-related toxicities (except alopecia) must ≤ Grade 1 at the time of randomization according to CTCAE version 4.03 (NCI 2009)

12. An adequate amount of tumor tissue (archived tumor tissue, or new biopsy if archived tissue is not available) must be available at the time of enrollment for central validation of BRAF V600 mutation and biomarker assessments

13. Subject has adequate bone marrow and organ function as defined by the following laboratory values without continuous supportive treatment (such as blood transfusion, coagulation factors and/or platelet infusion, or red/white blood cell growth factor administration) as assessed by laboratory for eligibility:

 Hematological

 Absolute neutrophil count ≥ 1.5 × 109/L

 Platelet count ≥ 100 × 109/L

 Hemoglobin ≥ 9 g/dL

 Coagulation

 PT/INR and PTT ≤ 1.5 x ULN. Subjects receiving anticoagulation treatment may be allowed to participate with INR established within the therapeutic range prior to randomization

 Renal

 Serum creatinine < 1.5 mg/dL

 Hepatic

 Total bilirubin ≤ 1.5 x ULN except for subjects with Gilbert’s syndrome who may only be included if the total bilirubin is ≤3.0 × ULN or direct bilirubin ≤1.5 × ULN

 Aspartate transaminase (AST) < 2.5 × ULN, except for subjects with liver metastasis, who are only included if the AST is < 5 × ULN

 Alanine transaminase (ALT) < 2.5 × ULN, except for subjects with liver metastasis, who are only included if the ALT is < 5 × ULN

 Albumin ≥ 2.5 g/dL

14. Left ventricular ejection fraction (LVEF) ≥ lower limit of institutional normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan

15. Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption Syndrome or major resection of the stomach or bowels

16. Subjects must avoid consumption of grapefruit, Seville oranges or products containing the juice of each during the entire study and preferably 7 days before the first dose of study medications, due to potential CYP3A4 interaction with the study medications. Orange juice is allowed.

Sonstiges

Kontaktpersonen

jenny.landsberg@ukbonn.de
karoline.wieczorek@med.uni-duesseldorf.de
Bernhard.Homey@med.uni-duesseldorf.de

Ausschlusskriterien

Exclusion criteria for all subjects

3. Subjects with uveal or mucosal melanoma

4. Prior systemic anti-cancer treatment (e.g., checkpoint inhibitors, targeted therapy [e.g., BRAF and/or MEK inhibitors], chemotherapy, biologic therapy, tumor vaccine therapy, or any systemic investigational treatment) for unresectable or metastatic melanoma.

5. Prior loco-regional treatment with intralesional therapy (e.g., talimogene laherparepvec) for unresectable or metastatic melanoma in the last 6 month prior to start of study treatment.

6. Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to start of study treatment (e.g., targeted therapy, immunotherapy [e.g., interferon], biochemotherapy, tumor vaccine).

7. Radiation therapy ≤ 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed ≤ 2 weeks prior to start of study treatment).

8. Major surgery, open biopsy, or significant traumatic injury ≤ 2 weeks prior to start of study treatment. Minor surgical procedures should be completed 7 days prior to start of study treatment.

9. Active, known or suspected autoimmune disease or a documented history of autoimmune disease, including ulcerative colitis and Crohn’s disease (Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll).

10. Systemic chronic steroid therapy (≥10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.

11. Current pneumonitis or interstitial lung disease.

12. History of organ transplant requiring use of immunosuppressive medication.

13. Taken an investigational drug ≤28 days or ≤5 half-lives (minimum 14 days) prior to start of study treatment, whichever is shorter.

14. History of severe hypersensitivity reactions to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.

15. Current use of a prohibited medication.

16. Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ.

17. Active infection requiring systemic antibiotic therapy within 2 weeks prior to start of study treatment.

18. Known history of testing positive for Human Immunodeficiency Virus (HIV) infection. For Germany only: testing positive for HIV during screening using a local test.

19. Subjects with active Hepatitis B infection (HbsAg positive) will be excluded. Note: Subjects with antecedent of Hepatitis B (anti-HBc positive, HbsAg and HBV-DNA negative) are eligible.

20. Subjects with positive test for hepatitis C ribonucleic acid (HCV RNA) Note: Subjects in whom HCV infection resolved spontaneously (positive HCV antibodies without detectable HCV-RNA) or those that achieved a sustained virological Response after antiviral treatment and show absence of detectable HCV RNA ≥ 6 months (with the use of IFN-free regimes) or ≥ 12 months (with the use of IFN-based regimes) after cessation of antiviral treatment are eligible

21. Any medical condition that would, in the investigator’s judgment, prevent the subject’s participation in the clinical study due to safety concerns, compliance with clinical study procedures or interpretation of study results.

22. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.

23. Uncorrectable electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), long QT syndrome or taking medicinal products known to prolong the QT interval.

24. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).

25. Pregnant or nursing (lactating) women confirmed by a positive hCG laboratory test within 72 hours prior to initiating study treatment. Note: Low levels of hCG may also be considered a tumor marker, therefore if low hCG levels are detected, another blood sample at least 4 days later must be taken to assess the kinetics of the increase and transvaginal ultrasound must be performed to rule out pregnancy.

26. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy including:

 Presence of predisposing factors to RVO or central serous retinopathy (e.g.,

uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension,

uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability

syndromes); or

 Visible retinal pathology as assessed by ophthalmic examination that is considered a

risk factor for RVO or central serous retinopathy such as:

 Evidence of new optic disc cupping;

 Evidence of new visual field defects on automated perimetry;

 Intraocular pressure >21 mmHg as measured by tonometry.

27. Cardiac or cardiac repolarization abnormality, including any of the following:

 History or current diagnosis of cardiac disease indicating significant risk of safety for subjects participating in the study such as uncontrolled or significant cardiac disease, including any of the following:

 Recent (within last 6 months) myocardial infarction (MI)

 Unstable angina (within last 6 months),

 Uncontrolled congestive heart failure (CHF)

 Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained

ventricular tachycardia, and clinically significant second or third degree

atrioventricular [AV] block without a pacemaker).

28. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 150-days after stopping treatment with PDR001. Highly effective contraception methods include: a. Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. b. Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. c. Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject. d. Placement of a non-hormonal intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year.

Notes:

 Double-barrier contraception: condom and occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal agent (foam/gel/cream/suppository) are not considered highly effective methods of contraception.

 Hormonal-based methods (e.g., oral contraceptives) are not considered as highly effective methods of contraception due to potential drug-drug interactions with dabrafenib.

 Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

29. Sexually active males unless they use a condom during intercourse while on treatment and for 150 days after stopping treatment with PDR001 and should not father a child in this period. A condom is required to be used by vasectomized men as well during intercourse in order to prevent delivery of the drug via semen.

Diagnosen

Malignes Melanom

Einschlusskriterien

siehe angehängtes Protokoll

Sonstiges

Ausschlusskriterien

Diagnosen

Malignes Melanom

Einschlusskriterien

18 Jahre oder älter

Lokal fortgeschrittenes, inoperables oder metastasiertes kutanes Melanom (Stadium IIIC oder IV nach AJCC)

Vorhandensein einer BRAF V600E/K Mutation im Tumorgewebe (vor Randomisierung)

Unbehandelte Patienten oder Patienten mit Progress nach einer first-line Immuntherapie im Stadium IIIC oder IV (adjuvante Vortherapie ist erlaubt, z.B. IFN- , IL -2-Therapie , andere Immuntherapie oder Bestrahlung)

Nachweis mindestens einer meßbaren Läsion (radiologisch oder fotografisch)

ECOG 0/1

Ausreichende Knochenmarks- und Organfunktion, Herz- und Laborparameter

Normales Funktionieren der Aktivitäten des täglichen Lebens

Sonstiges

Kontaktpersonen

jenny.landsberg@ukbonn.de

Ausschlusskriterien

Aktive oder instabile Hirnmetastase; Vorgeschichte einer leptomeningealen Metastasen

Nicht-kutanes Melanom

Vorgeschichte oder aktueller Nachweis einer zentralen serösen Retinopathie (CSR), Retinalvenenverschlusses (RVO) oder Vorgeschichte einer degenerativen Netzhauterkrankung

Jede frühere Anti-Krebs- Behandlung, umfangreiche Strahlentherapie oder Studienmedikamente für das lokal fortgeschrittene, inoperable oder metastasierte Melanom (adjuvante Vortherapie incl. Ipilimumab ist zulässig)

M. Meulengracht

Vortherapie mit einem BRAF-Inhibitor und / oder einem MEK –Inhibitor

Eingeschränkte Herz-Kreislauf -Funktion oder klinisch signifikante Herz-Kreislauferkrankungen

Diagnosen

Malignes Melanom

Einschlusskriterien

siehe angehängtes Protokoll

Sonstiges

Ausschlusskriterien

Diagnosen

Mastozytose

Einschlusskriterien

- Geschlecht:  Beide, männlich und weiblich
- Mindestalter:  18   Jahre

- Alle Mastozytosepatienten mit Erstdiagnose seit Januar 1990 in den teilnehmenden europäischen Zentren.

Sonstiges

Kontaktpersonen

tbruemmendorf@ukaachen.de

Ausschlusskriterien

Keine Ausschlusskriterien

Diagnosen

Plattenepithelkarzinom

Einschlusskriterien

Patient mit Resektion eines pathologisch bestätigten CSCC (nur primäre CSCC-Läsion oder primäres CSCC mit Knotenbefall oder CSCC-Knotenmetastase mit bekannter primärer CSCC-Läsion, die zuvor innerhalb des drainierenden Lymphknoten-Echelons behandelt wurde), mit makroskopischer Bruttoresektion der gesamten Erkrankung.

Sonstiges

Kontaktpersonen

ivonne.fischer@uk-koeln.de

Ausschlusskriterien

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