Phase 2 trial of Tepotinib in patients with metastatic solid cancer with c-MET amplification or MET gene mutation of exon 14
- Conditions
- Neoplasms
- Registration Number
- KCT0004498
- Lead Sponsor
- Chungbuk National University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 35
1)Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC)
2)Subjects who are not eligible for surgical and/or local-regional therapies or who have progressive disease (PD) after surgical and/or local-regional therapies
3)Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers
4)A tumor biopsy (excluding fine needle aspiration and cytology samples) is required for determining MET status (a fresh pretreatment tumor biopsy is recommended but archived tumor sample is acceptable).
MET+ status, as determined by the central laboratory is defined as c-MET exon 14 skipping mutation (981_1028splice, X1007_splice, X1008_splice, X1009_splice, X1010_splice, X963_splice, X1006_splice, 963_D1010splice, Y1003N, D1010H/N/Y), or c-MET copy number gain (=4.0) in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study PI, prior to study entry.).
5)Male or female, 19 years of age or older
6)Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). The target lesion that has received previous local therapy should not be considered as measurable unless clear progression has been documented since the therapy.
7)Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
8)Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment
9)Life expectancy judged by the Investigator of at least 3 months
1)Prior treatment with any agent targeting the HGF/c-MET pathway
2)Prior EGFR therapy for EGFR activating mutant NSCLC
3)Local-regional therapy within 4 weeks prior to Day 1 of trial treatment (e.g., major surgery, radiation therapy [with the exception of palliative radiotherapy (e.g. bone, brain) and radiotherapy administered to superficial lesions], hepatic arterial embolization, transcatheter arterial chemoembolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation)
NOTE: palliative radiotherapy (e.g. bone, brain) should be within a limited field of radiation and for palliation only; it should be a short course, according to local institutional recommendations, and should be completed at least 7 days prior to the first administration of trial treatment
4)Prior history of organ transplant
5)Laboratory index at baseline:
?Hemoglobin = 8.5 g/dL (without transfusion or growth factor support in the preceding 14 days)
?Neutrophils < 1.5 x 109/L
?Platelets < 100 x 109/L (without transfusion or growth factor support in the preceding 7 days)
?Total bilirubin > 3 mg/dL
?Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)
?Renal impairment as evidenced by serum creatinine = 1.5 x ULN, or calculated creatinine clearance (CrCl) < 40 mL/min by Cockroft-Gault formula (24-hour CrCl might be requested by the Investigator for confirmation, if calculated CrCl is < 40 mL/min. In such case, subjects with 24-hour CrCl < 40 mL/min should be excluded)
CrCl (mL/min) = [140 – age (year) x weight (kg)] / 72 x serum creatinine (mg/dL) {x 0.85 for female subjects}
?International normalized ratio (INR) > 2.3 (in accordance with the guidance that has been modified for Child-Pugh classification)
?Albumin < 28 g/L (without transfusion in the preceding 14 days)
6)Past or current history of neoplasm other than current cancer, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, node-negative thyroid cancer or other cancer curatively treated and with no evidence of disease for at least 5 years
7)Known central nervous system (CNS) or brain metastasis that is either symptomatic or untreated
8)Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested products
9)Clinically significant gastrointestinal bleeding within 4 weeks prior to Day 1 of trial treatment
10)Impaired cardiac function:
?Left ventricular ejection fraction <45% on recent echocardiography (Note: a screening left ventricular ejection fraction assessment without history of congestive heart failure is not required unless clinically indicated.)
?Serious arrhythmia
?Unstable angina pectoris
?Congestive heart failure New York Heart Association (NYHA) III and IV
?Myocardial infarction within the last 12 months prior to Day 1 of the trial treatment
?Symptomatic uncontrolled Pericardial effusion
11)Hypertension uncontrolled by standard therapies (not stabilized to = 150/90 mmHg)
12)Subject with a family history of long QT syndrome or who take any agent that is known to prolong QT/QTc interval or with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 450 msec)
13)Known human immunodeficiency virus (HIV) infection
14)Subjects who have acute pancreatitis and/or chronic pancreatitis, with elevated lipase and/or
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Objective response rates
- Secondary Outcome Measures
Name Time Method progression free survival;overall survival