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Study of AZD6094 (Volitinib) in Advanced Gastric Adenocarcinoma Patients With MET Amplification as a Third-line Treatment

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02449551
Recruitment Status : Recruiting
First Posted : May 20, 2015
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Jeeyun Lee, Samsung Medical Center

Brief Summary:

Volitinib is a potent and selective small molecule c-Met kinase inhibitor. Volitinib was found to inhibit c-Met kinase at the enzyme and cell levels with IC50s of 4 nM for both enzyme and Met phosphorylation in the cell. Consistent with its potent enzyme and cell activity, volitinib was found to inhibit cell growth in vitro against tumors with c-Met gene amplification in the absence of HGF stimulation with IC50s generally below 10 nM. It also potently inhibited HGF-stimulated cell proliferation against tumors with c-Met overexpression or carrying a HGF/c-Met autocrine loop.

This study is a single-arm, phase II study of votilinib in patients with advanced gastric adenocarcinoma harboring MET amplification as a third line treatment Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.

To investigate the efficacy of volitinib in patients with advanced gastric adenocarcinoma harboring MET amplification.


Condition or disease Intervention/treatment Phase
Advanced Gastric Adenocarcinoma Drug: Volitinib Phase 2

Detailed Description:
same as above

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Actual Study Start Date : February 10, 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: Volitinib
Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.
Drug: Volitinib
Volitinib is an orally available, potent, selective, small molecule c-MET inhibitor. Volitinib 800 mg will be administered orally once a day for 21 days as one cycle.
Other Name: AZD6094




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 8 weeks ]

Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 8 weeks ]
  2. Duration of response [ Time Frame: 8 weeks ]
  3. Disease control rate [ Time Frame: 8 weeks ]
  4. Overall survival (OS) [ Time Frame: 8 weeks ]
  5. Number of subjects with Adverse Events as a measure of safety and tolerability [ Time Frame: 8 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of fully informed consent prior to any study specific procedures.
  2. Patients must be ≥20 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.
  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.
  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. Eastern Cooperative Oncology Group 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)

Exclusion Criteria:

  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 (>Common Toxicity Criteria for Adverse Effects grade 1) caused by previous cancer therapy.
  9. Intestinal obstruction or Common Toxicity Criteria for Adverse Effects grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
  10. Resting ECG with measurable QTcB > 480 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02449551


Contacts
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Contact: yoon jeong Ahn 221487395 ext 82
Contact: Jee yun Lee, MD,Ph.D. 234103459 ext 82

Locations
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Korea, Republic of
Samsung Medical center Recruiting
Seoul, Korea, Republic of, 135-710
Contact: Yoonjeong Ahn    82-2-2148-7395    younjeong.ahn@samsung.com   
Principal Investigator: Jeeyun Lee, MD,PhD         
Sponsors and Collaborators
Samsung Medical Center
Investigators
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Principal Investigator: Jee yun Lee, MD,Ph.D. Samsung Medical Center,Seoul,Korea
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Responsible Party: Jeeyun Lee, MD,PhD, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT02449551    
Other Study ID Numbers: 2014-07-167
First Posted: May 20, 2015    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms