EUCTR2017-001491-35-ES进行中（未招募）1 期
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
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 165
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •a.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
- •b.The following solid tumour indications are allowed to be enrolled into Part A:
- •Breast cancer (TNBC, ER+/-, HER2+/-), gastrointestinal (GI) cancers (colorectal cancer, CCC, gastric cancer), ovarian cancer, cervical cancer, prostate cancer, NSCLC (lung adenocarcinoma), melanoma, sarcomas (osteosarcoma, liposarcoma, rhabdomyosarcoma, fibrosarcoma), desmoid tumours, adenoid cystic carcinoma, and glioblastoma multiforme (GBM)
- •c.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:
- •Hodgkin lymphoma (HL)
- •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), CNS lymphoma
- •Multiple myeloma (MM)
- •Specific criteria per type of lymphoma:
- •HL: relapsed/refractory to at least two lines of treatment, among which includes brentuximab vedotin
- •B-cell NHL: relapsed/refractory upon at least one line of chemo-immunotherapy, no standard therapy available
- •T-cell NHL: relapsed/refractory upon at least one line of chemotherapy, no standard curative therapy available
- •Specific criteria for multiple myeloma:
- •Relapsed/refractory to at least two lines of therapy, including both a proteasome inhibitor and an immunomodulatory agent (IMiD), and no standard alternative therapy available
- •d.Solid tumours: =1 measurable lesion according to RECIST v1.1 guideline for solid tumours
- •e.Lymphomas: =1 measurable lesion according to The Lugano Classification
- •f.Multiple myeloma: must have measurable disease (serum M-protein = 10 g/L or urine M-protein = 200 mg/24 hours or abnormal free light chain (FLC) ratio with involved FLC > 100 mg/L) or proven plasmacytoma by biopsy)
- •g.Patients in Part B: must have tumours characterised by activation of the NOTCH signalling pathway. All patients should have sufficient archival biopsy tissue not older than 6 months prior to pre-screening (or if not available-a fresh tumour biopsy must be taken)
- •h.Patients in Part B: willing to provide a fresh pre-dose and, if feasible, on-treatment and an EOT tumour biopsy
- •i.Patients in Part A: must have sufficient archival tumour tissue samples not older than 6 months prior to screening (or if not available a fresh pre-dose tumour biopsy)
- •2.Demography
- •a.Men and women = 18 years old on the day of signing informed consent
- •b.ECOG performance status 0 or 1
- •c.Patients able and willing to swallow capsules
- •3.Organ function and laboratory results
- •Patients must have the following laboratory values (obtained within 14d of enrolment):
- •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, 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)
排除标准
- •1.Medical History
- •a.Patients with symptomatic CNS metastases (neurologically unstable or requiring increasing doses of steroids to control their CNS disease)
- •b.Hypersensitivity to any of the excipients of CB-103
- •c.Patients with unresolved nausea, vomiting, or diarrhoea of CTCAE grade > 1
- •d.Impairment of GI function or presence of GI disease that may significantly alter the absorption of CB-103
- •e.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
- •a.Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
- •1.Clinically significant cardiac disease including congestive heart failure (NYHA class III or IV), arrhythmia or conduction abnormality requiring medication, or cardiomyopathy
- •2.Clinically uncontrolled hypertension (blood pressure > 160/110 mmHg)
- •3.Complete left bundle branch block
- •4.Right bundle branch block + left anterior hemiblock
- •5.Mandatory use of a cardiac pacemaker
- •6.Congenital long QT syndrome
- •7.History or presence of sustained or symptomatic ventricular tachyarrhythmia
- •8.Presence of unstable atrial fibrillation (ventricular response > 110 bpm)
- •9.Clinically significant resting bradycardia (< 50 bpm)
- •10.Corrected QTcF > 450 ms for males and > 470 ms for females at the screening ECG
- •11.QRS = 110 ms
- •12.History of symptomatic congestive heart failure
- •13.LVEF < 50%. History of absolute decrease in LVEF of = 15 absolute %, or = 10 absolute % and crossing from > LLN to < LLN on prior anti-HER2 therapy, even if asymptomatic
- •14.Angina pectoris = 6 months prior to starting CB-103
- •15.Acute myocardial infarction = 6 months prior to starting CB-103
- •b.General conditions or other clinically significant diseases, including any one of the following:
- •1.Haemorrhagic, embolic, or thrombotic stroke within 6 months prior to the first planned CB-103 infusion
- •2.Prior allogeneic bone marrow/haematopoietic stem cell transplant
- •3.Autologous haematopoietic stem cell transplant = 6 months prior to starting study drug
- •4.Known infection with HIV or hepatitis B or C requiring treatment
- •5.Any active infection requiring the use of parenteral anti-microbial agents or > Grade 2
- •6.Non-malignant interstitial lung disease or pneumonitis
- •7.Dyspnoea of any cause requiring supplemental oxygen therapy and dyspnoea at rest due to complications of advanced malignancy and co-morbidities
- •8.Significant traumatic injury or major surgery within 14d of scheduled dosing day 1
- •9.Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol
- •3.Prior Therapy
- •a.Cytotoxic chemotherapy within 3 weeks (6 weeks for nitrosoureas and mitomycin C) of scheduled first dose of CB-103 on day 1
- •b.Prior cumulative doxorubicin exposure of = 450 mg/m2
- •c.Prior cumulative epirubicin exposure of = 900 mg/m2
- •d.Any investigational treatment within 4 weeks of scheduled CB-103 dosing day 1.
- •e.Prior treatment with any NOTCH signalling inhibitor compound
- •f.Concurrent enrolment in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo
- •g.Radiation therapy within 2 weeks of scheduled CB-1
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