A phase 1b/2 study of tepotinib in combination with paclitaxel in patients with MET amplified or MET exon 14 alterated advanced gastric and gastroesophageal junction carcinoma
- Conditions
- Neoplasms
- Registration Number
- KCT0006691
- Lead Sponsor
- Hallym University Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot yet recruiting
- Sex
- All
- Target Recruitment
- 42
1.Have the willingness to sign a written informed consent document prior to any study specific precedures
2.Age = 19 years of male and female
3.At each phase of the trial, subjects who meet the following requirements in the appropriate phase will be enrolled.
A.Phase 1b: Subjects with a histologically confirmed metastatic solid tumor that have progressed after treatment with approved therapies or for which there is no standard effective therapy available.
B.Phase 2b: Subjects with histologically confirmed locally advanced or metastatic gastric and gastroesophageal carcinoma that have progressed after treatment with first-line fluoropyrimidine-based chemotherapy, with MET amplified (copy number gain =3) or MET exon 14 skipping mutation in the archival or fresh tumor tissue specimen identified in our customized targeted DNA deep sequencing (NGS by gastric cancer panel). If the subject received adjuvant chemotherapy after curative gastric resection and lymph node dissection, adjuvant chemotherapy is considered to be the first-line palliative chemotherapy if the disease recurred during adjuvant chemotherapy or within 6 months after the completion of adjuvant chemotherapy.
4.Patients must have measurable disease based on RECIST 1.1 (Phase 2 part only)
Measurable disease will not be required for enrollment in the phase1b part. Patients with evaluable lesion only (without measurable lesion) can be enrolled in the phase 1b part.
5.ECOG performance status 0-1
6.Patients must have adequate organ and marrow function as defined below:
A.Absolute neutrophil count (ANC) = 1.5 x 109/L,
B.Hemoglobin = 9.0 g/dL,
C.Platelet = 100 x 109/L,
D.AST and/or ALT = 3 × upper limit of normal (ULN)
[Regardless of the presence of liver metastases, only subjects who have AST/ALT = 3 × ULN can be enrolled in phase 1b part; In phase 2 part, subjects with AST and/or ALT = 5 X ULN can be enrolled if they have liver metastases]
E.Total bilirubin: = 2 × ULN; Subjects with a bile duct obstruction will be eligible if they meet the criteria after appropriate bile drainage; Patients with Gilbert syndrome should also be registered after confirming that the total bilirubin level is within the normal range through a follow-up screening test)
F.Alkaline phosphatase: = 2 × ULN
G.Serum creatinine clearance) > 50mL/min (by Cockcroft-Gault formula, MDRD, CKD-EPI formula or 24hr urine collection)
7.Patients must be able to swallow and retain oral medications
8.Serum ß-HCG test negative within 14 days before the first administration (women of childbearing potential only).
9.Requirement for contraception
? Women of child-bearing potential (All women who have physiological potential to be pregnant unless adequate contraception is used during the study treatment and the 4 weeks followng the discontinuation of the study treatment); subjects can be enrolled if they use the following effective contraceptive methods:
•Subjects must abstain from any form of sexual intercourse if the complete abstinece is preferred and consistent with their daily lifestyle. Periodic abstinence (eg, calendar rhythm method, symptothermal method, etc) and external ejaculation methods are not acceptable contraceptive methods.
•Sterilization procedure for women: surgical bilateral ovariectomy with or without hysterectomy; tubal ligation at least 6 weeks prior to enrollment into this study. Bilateral ovariectomy alone is allowed a subject whose reproductive status is
1.Active central nervous system (CNS) lesions (ie, those with radiologically unstable or symptomatic brain lesions). For those who receive radiation or surgical treatment, the subject can be enrolled if the subject is maintained without evidence of CNS disease progression for more than 4 weeks. However, patients with a leptomeningeal metastasis are excluded.
2.Treatment with any of the following:
•Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
•Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the subject received an investigational drug from another clinical trial, the subejct can be enrolled after 2 weeks of last administration and more than 5 x half–life of the investigational drug. If monoclonal antibody therapy was given, the subject can be enrolled after four weeks after the last does.
•Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment. If acute symptoms of radiation have fully resolved, the extent and timing of radiotherapy for eligibility can be discussed between the local investigator and principal investigator.
•Any previous exposure to a c-MET inhibitor
3.History of allogeneic bone marrow transplantation or organ transplantation
4.History of another primary cancer (excluding gastric cancer):
Exceptions are:
•Adequately treated non-melanoma skin cancer (basal cell or squamous cell carcinoma), curatively treated in situ cancer of the cervix, completely resected thyroid cancer without distant metastasis in which all treatment has been completed (Appropriate wound healing is required prior to clinical trial enrollment)
•Other curatively treated solid tumors except for gastric cancer with no evidence of disease recurrence at least 36 months before participating in this trial
5.Clinically significant cardiovascular disease including but not limited to:
•Acute coronary syndome within the 6 months prior to the initiation of study drug (including myocardial infarction or unstable angina, Coronary Artery Bypass Graft surgery, percuatneous coronary intervention and stenting)
•Current heart failure or past history of heart failure
•Left ventricle ejection fraction (LVEF) < 50%; if there is no past history of heart failure, screening with echocardiography to confirm EF is not required.
• Current or past history of clinically significant cardiac arrhythmia (eg, complete left bundle branch block, third degree heart block)
•Any risk factors that prolong QTc or increase the probability of arrhythmia, including medication (eg: heart failure, hypokalemia, congenital long QT syndrome, history of Torsades de Pointes)
6.Persistent uncontrolled hypertension as defined by: systolic >180 mmHg or diastolic >100 mmHg despite medical treatment
7.Seropositivity of HIV or known active hepatitis B and/or active hepatitis C infection. Hepatitis B carriers may be enrolled if prophylactic use of an antiviral agent with minimal interaction with CYP3A4 is administered to inhibit HBV activation (eg. Entecavir, adefovir)
8.Impairment of gastrointestinal function or gastrointestinal disorders (eg. untreated ulcerative disorders; uncontrolled nausea, vomiting, or diarrhea; absorption disorder syndrome; small bowel resection; ileostomy). Patients with ileostomcy will not allowed to be enrolled, but patients with colostomy can be enro
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Phase 1b: MTD and RP2D / Phase 2: 4-month PFSR
- Secondary Outcome Measures
Name Time Method Phase 1b: DLT, Safety, preliminary antitumor activity / Phase 2: ORR, TTR, DOR, DCR, PFS, OS, Safety, and tolerability