Study of Volitinib in advanced gastric adenocarcinoma patients with MET amplification as third-line treatment
- Conditions
- Neoplasms
- Registration Number
- KCT0004070
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 15
1. Provision of fully informed consent prior to any study specific procedures.
2. Patients must be =18 years of age.
3. Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after second-line therapy.
- Both fluoropyrimidine and platinum agent need to be contained in the prior chemotherapies
- Prior adjuvant or neoadjuvant therapy is counted as 1 regimen, provided that disease progression occurs within 6 months after the completion of adjuvant or neoadjuvant therapy.
- That is refractory to standard therapy or for which no standard therapy is availabile or accessible patially.
- Acceptable prior chemotherapy regimens for this protocol are chemotherapy regimens that include Immune Target agent therapy. (such as a pembrolizumab, ramucirumab etc)
4. Have the presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
5. Patients with MET amplification through the VIKTORY trial. (The VIKTORY trial uses Ion Torrent PGM to screen for a panel of cancer mutations and nanostring, copy number variation panel (see addendum for the VIKTORY trial)
6. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
7. ECOG performance status 0-1.
8. Patients must have a life expectancy = 3 months from proposed first dose date.
9. Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
- Haemoglobin =9.0 g/dL (transfusion allowed)
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- White blood cells (WBC) > 3 x 109/L
- Platelet count =100 x 109/L (transfusion allowed)
- Total bilirubin = 1.5 x institutional upper limit of normal (ULN) (does not include patients with Glibert’s disease)
- AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be = 5x ULN
- Serum creatinine =1.5 x institutional ULN
10. At least one measurable lesion that can be accurately assessed by imaging or physical examination at baseline and following up visits.
11. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1. for women of childbearing potential.
12. Provision of consent for mandatory biopsy at progression (fresh frozen will be mandatory if clinically feasible)
13. Provision of archival or fresh tissue sample at baseline (fresh frozen will be mandatory if clinically feasible)
14. Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of AZD6094, medications known to be potent inhibitors of CYP1A2 or CYP3A4, potent inducers of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range (Appendix E)
1.Are currently enrolled in, or discontinued within the last 21 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
2. Any previous treatment with MET inhibitors
3. Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for =5 years.
4. HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
5. Patients unable to swallow orally administered medication.
6. Treatment with any investigational product during the last 21 days before the enrollment (or a longer period depending on the defined characteristics of the agents used).
7. Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 3 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates or denusomab for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment.
8. With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by previous cancer therapy.
9. Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
10. Mean resting corrected QT interval changed to exclude QTcF*>470msec for women and >450msec for men, obtained from 3 electrocardiograms (ECGs) or factors that may increase the risk of QTc prolongation such as chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first- degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
*QTc interval must be calculated using Fridericia’s correction (QTcF)
11. Patients with cardiac problem as follows: uncontrolled hypertension (BP =150/95 mmHg despite medical therapy) Baseline Left ventricular ejection fraction below the LLN of <55% measured by echocardiography or institution’s LLN for MUGA, Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest , Symptomatic heart failure (NYHA grade II-IV), Prior or current cardiomyopathy, Severe valvular heart disease, Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy), Acute coronary syndrome within 6 months prior to starting treatment
12. Female patients who are breast-feeding or child-bearing and Male or female patients of reproductive potential who are not employing an effective method of contraception
13. Any evidence of severe or uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant, including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
14. Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of AZD6094, medications known to be potent inhibitors of CYP1A2 or CYP3A4, potent inducers of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range (Appendix E)
ADD SECTION ON RESTRICTIONS
The following restrictions apply while the patient is receiving study treatment and for th
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS)
- Secondary Outcome Measures
Name Time Method Objective response rate (ORR);Duration of response;Disease control rate;Overall survival (OS);Adverse Events