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NCT03422679 | SNCTP000002662

Studio volto a valutare la sicurezza, la tollerabilità, i livelli nel sangue e l’efficacia del farmaco in studio CB-103 preso per via orale in pazienti adulti affetti da alcuni tipi di tumori

Datenbasis: BASEC (Import vom 25.06.2019), WHO (Import vom 23.06.2019)
Geändert: 17.06.2019
Krankheitskategorie: Anderer Krebs

Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)

Questo studio è concepito per ottenere informazioni sulla sicurezza e l’efficacia di un farmaco sperimentale chiamato CB-103 quando viene somministrato a pazienti umani come trattamento per tumori solidi in stadio avanzato o metastatico e tumori del sangue caratterizzati da alterazioni della via di segnalazione di NOTCH.
Questo studio è stato perciò sviluppato per analizzare il grado di sicurezza e tollerabilità di CB-103 e per ottenere maggiori informazioni sugli effetti indesiderati.
Lo studio si propone inoltre di stimare la più alta dose che i pazienti adulti sono in grado di tollerare.
Il farmaco in studio è un farmaco orale fornito in forma di capsule contenute in un flacone

Untersuchte Krankheiten (Datenquelle: BASEC)

Tumori solidi (masse anomale di tessuto a crescita incontrollata) in stadio avanzato o metastatico (ovvero quando il tumore si diffonde da una parte del corpo ad un'altra) e tumori del sangue caratterizzati da alterazioni della via di segnalazione di NOTCH.
La via di segnalazione di NOTCH è un meccanismo di comunicazione da cellula a cellula presente nel corpo umano che, una volta attivato, potrebbe promuovere la proliferazione e la crescita del tumore.

Health conditions (Datenquelle: WHO)

Breast Cancer;Colorectal Cancer;Cholangiocellular Carcinoma;Sarcoma;Desmoid Tumour;Adenoid Cystic Carcinoma;Non-hodgkin Lymphoma

Seltene Krankheit (Datenquelle: BASEC)

Nein

Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne) (Datenquelle: BASEC)

Farmaco orale CB-103

Interventions (Datenquelle: WHO)

Drug: CB-103

Kriterien zur Teilnahme an der Studie (Datenquelle: BASEC)

Pazienti con tumori solidi istologicamente o citologicamente confermati che siano non resecabili chirurgicamente, localmente avanzati o metastatici la cui malattia sia progredita durante almeno una linea di terapia sistemica e per i quali non esistano terapie curative standard:
• Tumore mammario (tumore mammario triplo negativo [triple negative breastcancer, TNBC], ER+/-, HER2+/-), tumori gastrointestinali (GI) (tumore del colon-retto [CRC], carcinoma colangiocellulare [CCC]), sarcomi (osteosarcoma, liposarcoma, rabdomiosarcoma, fibrosarcoma), tumori desmoidi, carcinoma adenoide cistico e tumore glomico maligno.

Pazienti con tumori maligni ematologici avanzati, istologicamente o citologicamente confermati, la cui malattia abbia manifestato una recidiva o una progressione durante una terapia standard e per i quali a questo punto non esista alcuna terapia standard:
• Linfomi non Hodgkin [NHL]: linfoma follicolare [FL], linfoma diffuso a grandi cellule B [DLBCL], linfoma di Burkitt, linfoma della zona marginale nodale NMZL], linfoma splenico della zona marginale [SMZL], linfoma a cellule mantellari [MCL], linfoma a cellule T periferiche [PTCL], linfoma anaplastico a grandi cellule [ALCL, ALK-positivo e ALK-negativo].

I pazienti della Parte A (incremento della dose) devono disporre di campioni di tessuto tumorale d’archivio sufficienti; se non disponibili, deve essere effettuata una nuova biopsia del tumore. I pazienti saranno incoraggiati a sottoporsi a una nuova biopsia tumorale prima della somministrazione e, se possibile, durante il trattamento e alla fine del trattamento (EOT)

Ausschlusskriterien (Datenquelle: BASEC)

- Funzione cardiaca ridotta o cardiopatie clinicamente significative
- Terapia concomitante con alcune classi di medicinali, tra cui quelli che prolungano l’intervallo QT
- Tossicità non risolta di grado CTCAE > 1 derivante da una precedente terapia antitumorale o radioterapia (escluse neurotossicità, alopecia, ototossicità, linfopenia) o recupero incompleto da una precedente chirurgia, salvo consenso documentato di Cellestia e dello sperimentatore principale

Inclusion/Exclusion Criteria (Datenquelle: WHO)


INCLUSION CRITERIA:

1. Disease

- Patients with histologically or cytologically confirmed solid tumours that are
surgically unresectable, locally advanced, or metastatic and whose disease has
progressed on at least one line of systemic therapy and for whom no standard
curative therapy exists.

- The following solid tumour indications are allowed to be enrolled into Part A of
this study (dose escalation) based on known involvement of the NOTCH pathway
activation in these indications: Breast cancer (triple negative breast cancer
[TNBC], ER+/-, HER2+/-), gastrointestinal (GI) cancers (colorectal cancer [CRC],
cholangiocellular carcinoma [CCC]), sarcomas (osteosarcoma, liposarcoma,
rhabdomyosarcoma, fibrosarcoma), desmoid tumours, adenoid cystic carcinoma, and
malignant glomus tumour.

- Patients with histologically or cytologically confirmed, advanced haematological
malignancies) whose disease has relapsed or progressed upon standard therapy and
for whom at that point no standard therapy exists: Non-Hodgkin lymphomas (NHL):
Follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Burkitt
lymphoma, marginal zone B cell lymphoma (MZCL), splenic marginal zone lymphoma
(SMZL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), anaplastic
large cell lymphoma (ALCL).

2. Demography Men and women = 18 years old on the day of signing informed consent.

3. Organ function and laboratory results

Patients must have the following laboratory values:

a.ANC = 1.5x10^9/L (solid tumour indications) or = 1.0x10^9/L (haematological
malignancies) b.Haemoglobin (Hgb) = 10 g/dL (= 100 g/L) c.Platelet count = 75 x 109/L
(no platelet transfusion or growth factor support in the preceding 7d) d.Total serum
bilirubin = 1.5xULN e.ALP = 2.5xULN (if abnormalities are due to the underlying
malignancy and known bone metastases, then ALP must be = 5xULN) f.AST/SGOT and
ALT/SGPT = 2.5xULN (if abnormalities are due to the underlying malignancy and known
hepatic metastases, AST and ALT must be = 5xULN) g.Serum creatinine = 1.5xULN (if
serum creatinine > 1.5xULN, then serum creatinine clearance (CrCl) = 50 mL/min h to k:
Potassium, Total calcium (corrected for serum albumin), Magnesium and Phosphorus
levels: within normal limits or correctable with supplements l.Serum albumin
concentration = 30 g/L m.Serum amylase and serum lipase = ULN n.PTT = 1.5 x ULN and
INR = 1.3 (unless receiving therapeutic anticoagulants)

4. Contraceptive measures

- Women of childbearing potential and men must agree to use at least two highly
effective forms of contraception throughout the entire clinical trial period and
for 90d post-treatment completion.

- Men whose partners could be of childbearing potential must routinely use a condom
throughout the clinical trial period and for 90d posttreatment completion. The
partner should also use a reliable form of contraception.

5. Signed informed consent

EXCLUSION CRITERIA

1. Medical History

1. Patients with symptomatic CNS metastases (neurologically unstable or requiring
increasing doses of steroids to control their CNS disease)

2. Hypersensitivity to any of the excipients of CB-103

3. Patients with unresolved nausea, vomiting, or diarrhoea of CTCAE grade > 1

4. Impairment of GI function or presence of GI disease that may significantly alter
the absorption of CB-103

5. History of second or other primary cancer with the exception of:

- Curatively treated non-melanomatous skin cancer

- Curatively treated cervical cancer or breast carcinoma in situ

- Other primary solid tumour treated with curative intent and no known active
disease present and no treatment administered during the last 2 years.

2. Exclusionary concurrent medical conditions Impaired cardiac function or clinically
significant cardiac diseases.

3. Prior Therapy

- Cytotoxic chemotherapy within 3 weeks

- Any investigational treatment (including NOTCH signaling inhibitors and prior
treatment with CB-103) within 4 weeks of scheduled CB-103 dosing day 1

- Concurrent enrolment in another therapeutic clinical trial involving ongoing
therapy with any investigational or marketed product or placebo

- Radiation therapy within 2 weeks of scheduled CB-103 dosing day 1

- Immunotherapy, biological therapies, targeted small molecules, hormonal therapies
within 3 weeks of scheduled CB-103 dosing day 1

- Unresolved toxicity CTCAE grade > 1 from previous anti-cancer therapy or
radiotherapy (excluding neurotoxicity, alopecia, ototoxicity, lymphopenia), or
incomplete recovery from previous surgery.

4. Current medications

- Drugs which prolong QT interval

- Acid reducing agents

- Patients receiving warfarin and phenytoin that cannot be discontinued at least
one week prior to start of treatment with CB-103 and for the duration of the
study

- Anticoagulants.

5. Demography

- Patients who are pregnant or breast feeding.

6. Others - Patients who are unable or unwilling to comply with all study requirements
for clinical visits, examinations, tests, and procedures.

Weitere Angaben zur Studie im WHO-Primärregister

https://clinicaltrials.gov/show/NCT03422679

Weitere Angaben zur Studie aus der Datenbank der WHO (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03422679

Weitere Informationen zur Studie

Registrationsdatum der Studie

19.01.2018

Einschluss der ersten teilnehmenden Person

05.12.2017

Rekrutierungsstatus

Recruiting

Wissenschaftlicher Titel (Datenquelle: WHO)

A Phase I/IIA, Multi-Centre, Open-Label, Dose-Escalation Study With Expansion Arms to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of CB-103 Administered Orally in Adult Patients With Advanced or Metastatic Solid Tumours and Haematological Malignancies Characterised by Alterations of the NOTCH Signalling Pathway

Studientyp (Datenquelle: WHO)

Interventional

Design der Studie (Datenquelle: WHO)

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

Phase (Datenquelle: WHO)

Phase 1/Phase 2

Primäre Endpunkte (Datenquelle: WHO)

Part B: antitumour efficacy

Sekundäre Endpunkte (Datenquelle: WHO)

Part A: preliminary antitumour efficacy;Part A and B: pharmacokinetic - t1/2;Part A and B: pharmacokinetic - AUC;Part A and B: pharmacokinetic - tmax;Part A and B: pharmacokinetic - Cmax

Kontakt für Auskünfte (Datenquelle: WHO)

Please refer to primary and secondary sponsors

Studiendurchführungsorte

Durchführungsorte in der Schweiz (Datenquelle: BASEC)

Bellinzona

Durchführungsländer (Datenquelle: WHO)

Netherlands, Spain, Switzerland

Kontakt für weitere Auskünfte zur Studie

Angaben zur Kontaktperson in der Schweiz (Datenquelle: BASEC)

Michael Bauer
+41 61 633 2980
michael.bauer@cellestia.com

Kontakt für allgemeine Auskünfte (Datenquelle: WHO)

Dirk Weber, MD
+41 79 9441580
dirk.weber@cellestia.com

Kontakt für wissenschaftliche Auskünfte (Datenquelle: WHO)

Dirk Weber, MD
+41 79 9441580
dirk.weber@cellestia.com

Studienverantwortliche

Hauptsponsor (Datenquelle: WHO)

Cellestia Biotech AG

Weitere Studienidentifikationsnummern

BASEC ID (Datenquelle: BASEC)

2017-01238

Secondary ID (Datenquelle: WHO)

CB103-C-101