Pilot Study of Antiviral Treatment in Combination With Low-dose Gemcitabine in EBV-associated Gastric Cancer (EBVaGC)

Gastric Cancer Clinical Trial

Official title:

Pilot Study of Antiviral Treatment in Combination With Low-dose Gemcitabine in EBV-associated Gastric Cancer (EBVaGC)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05431244
• Other study ID #: 2022-03-110
• Status: Withdrawn
• Phase: N/A
• Start date: July 1, 2022
• Est. completion date: July 1, 2024

Study information

• Verified date: October 2022
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Epstein-Barr virus (EBV) is a double-stranded DNA human gamma herpes virus that establishes a persistent infection in over 90% of individuals. Most infections are self-limiting, but some cases are associated with the development of malignancies of lymphoid or epithelial origin. EBV-associated gastric carcinomas (EBVaGC) make up about 9% of all stomach cancers.

The constant presence of the viral genome in EBVaGC suggests the applicability of novel EBV-targeted therapies.

The antiviral nucleoside drug, (val)ganciclovir (GCV), is effective only in the context of the viral lytic cycle in the presence of EBV-encoded thymidine kinase (TK)/ protein kinase (PK) expression. JM Lee et al. reported that gemcitabine was lytic inducer via activation of the ATM/p53 genotoxic stress pathway in EBVaGC and confirmed the efficacy of gemcitabine-GCV combination treatment.

So we planned this proof of concept trial to apply the antiviral agent in EBVaGC.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 1, 2024
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Patients must be =20 years of age.

• Advanced gastric adenocarcinoma (including GEJ) that has progressed during or after second-line therapy.

• The patient's tumor tissue must have the pre-defined characteristics as follows ; EBV+

• ECOG performance status 0-1

• Patients must have a life expectancy = 4 months from proposed first dose date.

• The patient has measureable or evaluable disease as determined by standard computed tomography (CT) or magnetic resonance imaging (MRI) imaging. Examples of evaluable, nonmeasurable disease include gastric, peritoneal, or mesenteric thickening in areas of known disease, or peritoneal nodules that are too small to be considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1)

• Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below: WBC = 3,500 cells/mm3 and = 50,000 cells/mm3, ANC = 1,500 cells/mm3, Hemoglobin = 9 g/dL (transfusion allowed), Platelet count = 100,000 /mm3; Total bilirubin = 1.5 X ULN, 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; Creatinine clearance =60 mL/min

• Provision of fully informed consent prior to any study specific procedures.

Exclusion Criteria:

• The patient has a history severe or unstable heart disease, e.g. coronary artery disease requiring increased dose of anti-anginal medication and/or coronary angioplasty (including stent placement) within 24 months ( congestive heart failure NYHA III or IV, unstable angina, history of myocardial infarction within the last 12 months, clinically significant arrhythmia)

• The patient is pregnant or breastfeeding.(For women with pregnancy potential, an effective method of contraception should be agreed.)

• The patient has ongoing Uncontrolled systemic diseases (diabetes, hypertension, hypothyroidism, infection, etc.)

• The patient has ongoing central nervous system malignancy. (except for lesions that have been completely removed or underwent anterior brain radiotherapy/gamma knife procedure)

• The patient has a history of allergic reactions to gemcitabine, Valganciclovir, aciclovir, valacyclovir ganciclovir

• Patients with interstitial pneumonia or pulmonary fibrosis with clinical symptoms

Related Conditions & MeSH terms

• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Antiviral treatment in combination with low-dose gemcitabine
-maximun 6 cycles Gemcitabine; 30mg/m2 or 100mg/m2 or 300mg/m2 D1,D8, D15 (Q 1 week,3 times, rest for 1 week, every 4 weeks ) 1,2 cycle Valganciclovir; 900mg D8~D28 (from 1 week after Gemcitabine iv started, qd, PO, 21days) 3~6cycle Valganciclovir; 900mg D1~D28 (from Gemcitabine start date, PO, 28days)

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	Modified RECIST 1.1 criteria will be used to assess patient response to treatment by determining PFS and ORR. The modified RECIST 1.1 guidelines for measurable, non-measurable, target and non-target lesions and the objective tumour response criteria	up to 24months
Secondary	Best Overall Response Rate (BOR)	Modified RECIST 1.1 criteria will be used to assess patient response to treatment by determining PFS and ORR. The modified RECIST 1.1 guidelines for measurable, non-measurable, target and non-target lesions and the objective tumour response criteria	up to 24months