NL-OMON48760撤回不适用
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 - CB103-C-101
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 入组人数
- 33
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 64（—）
入选标准
- •1. Disease
- •a. Patients with histologically or cytologically confirmed solid tumours that are surgically unresectable, locally advanced, or metastatic 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 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.
- •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:
- •Non-Hodgkin lymphomas (NHL): Follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, nodal marginal zone lymphoma (NMZL), splenic marginal zone lymphoma (SMZL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), anaplastic large cell lymphoma (ALCL, ALK-positive and ALK-negative)
- •Specific criteria per type of lymphoma:
- •B-cell non-Hodgkin lymphoma: relapsed/refractory upon at least one line of chemo-immunotherapy, no standard therapy available.
- •T-cell non-Hodgkin lymphomas: relapsed/refractory upon at least one line of chemotherapy, no standard curative therapy available.
- •d. Patients with solid tumours must have at least one measurable lesion (at least 1.0 cm in diameter) according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 guideline for solid tumours (irradiated lesions are only measurable if unequivocal disease progression is demonstrated).
- •e. Patients with lymphomas must have at least one measurable lesion (at least 1.5 cm in diameter) according to *The Lugano Classification* for lymphomas.
- •f. Only for patients in Part B (dose expansion): patients must have tumours characterised by activation of the NOTCH signalling pathway (either by mutations, amplification/translocations or gene/protein expression alteration) validated by molecular and/or biochemical biomarkers assessed by using established methods at the central laboratory. 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) in order to enable the selection of the patients.
- •g. Only for patients in Part B (dose expansion): willing to provide a fresh pre-dose and, if feasible, on-treatment and an end of treatment (EOT) tumour biopsy.
- •h. Patients in Part A (dose escalation) must have sufficient archival tumour tissue samples preferably 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. Eastern Cooperative Oncology Group (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 14 days of enrolment):
- •a. Absolute neutrophil count (ANC) >= 1.5 x 109/L for patients with solid tumour indications
排除标准
- •1. Medical History
- •a. Patients with symptomatic CNS metastases who are neurologically unstable or require increasing doses of steroids to control their CNS disease.
- •Note: Patients with controlled CNS metastases may participate in this study. The patient must have completed radiotherapy or surgery for CNS metastases > 2 weeks prior to study entry. Patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on recent CNS imaging. If patients require steroids for management of CNS metastases, they must have been on a stable dose of steroids for two weeks preceding study entry.
- •Note: Patients without clinical signs or symptoms of brain involvement are not required to have a computed tomography (CT)/magnetic resonance imaging (MRI) scan of the brain.
- •b. Hypersensitivity to any of the excipients of the finished drug CB-103
- •c. Patients with unresolved nausea, vomiting, or diarrhoea of common terminology criteria for adverse events (CTCAE) grade * 1
- •d. Impairment of GI function or presence of GI disease that may significantly alter the absorption of CB-103 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection)
- •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 (New York Heart Association [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 atrial fibrillation
- •9. Clinically significant resting bradycardia (< 50 bpm)
- •10. Corrected QT interval using Fridericia formula (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. Left ventricular ejection fraction (LVEF) < 50%. History of absolute decrease in LVEF of >= 15 absolute percentage points, or >= 10 absolute percentage points and crossing from > lower limits of normal (LLN) to < LLN on prior anti-HER2 therapy, even if asymptomatic
- •14. Angina pectoris <= 6 months prior to starting study drug
- •15. Acute myocardial infarction (MI) <= 6 months prior to starting study drug
- •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 human immunodeficiency virus (HIV);
研究者
相似试验
进行中（未招募）
1 期
A Study to Assess the Safety, Tolerability, Blood levels and Efficacy of oral test drug CB-103 in Adult Patients with certain types of cancerEUCTR2017-001491-35-ESCellestia Biotech AG165
进行中（未招募）
1 期
A Study to Assess the Safety, Tolerability, Blood levels and Efficacy of oral test drug CB-103 in Adult Patients with certain types of cancerEUCTR2017-001491-35-NLCellestia Biotech AG165
进行中（未招募）
1 期
A Study to Assess the Safety, Tolerability, Blood levels and Efficacy of oral test drug CB-103 in Adult Patients with certain types of cancerocally advanced or metastatic solid tumours and relapsed or refractory T-cell acute lymphoblastic leukaemia or T-cell lymphoblastic lymphoma that show Notch pathway activation.MedDRA version: 21.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10066105Term: T-cell lymphoblastic leukaemia acuteSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10025236Term: Lymphoblastic lymphoma (Precursor B-lymphoblastic lymphoma/leukaemia)System Organ Class: 100000004864EUCTR2017-001491-35-DECellestia Biotech AG240
已完成
1 期
A Phase I/IIa, Open-Label, Multicentre, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of the Human Anti-CD38 Antibody MOR03087 as Monotherapy and in Combination with Standard Therapy in Subjects with Relapsed/Refractory Multiple MyelomaC90.0Multiple myelomaDRKS00003145MorphoSys AG91
尚未招募
不适用
A Phase 1a/1b, Multi-Centre, Open-Label, Dose-Escalation and Dose-Expansion Study in Patients with Solid Tumour Malignancies to Evaluate GEH200520 Injection / GEH200521 (18F) Injection Safety and Tolerability, Positron Emission Tomography Imaging, Pharmacokinetics, and Changes in Imaging after Treatmentirresectable or metastatic solid tumour or a local and resectable head and neck squamous cell carcinomahead and neck SCCPET scan bij solid tumorsNL-OMON53493GE Healthcare Ltd.50