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

October 31, 2022 updated by: Jeeyun Lee, Samsung Medical Center

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Antiviral treatment in combination with low-dose gemcitabine

For 1st & 2nd cycle D1, 8, 15 Gemcitabine 30-300mg/m2 IV over 30 minutes D8-28 Valganciclovir 900mg qd Every 4 weeks

For 3rd ~ 6th cycle D1, 8, 15 Gemcitabine 30-300mg/m2 IV over 30 minutes D1-28 Valganciclovir 900mg qd Every 4 weeks
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: up to 24months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response Rate (BOR)
Time Frame: up to 24months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Investigators

  • Principal Investigator: Jeeyun Lee, M.D. Ph.D, Samsung Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2022

Primary Completion (Anticipated)

July 1, 2024

Study Completion (Anticipated)

July 1, 2024

Study Registration Dates

First Submitted

June 13, 2022

First Submitted That Met QC Criteria

June 21, 2022

First Posted (Actual)

June 24, 2022

Study Record Updates

Last Update Posted (Actual)

November 1, 2022

Last Update Submitted That Met QC Criteria

October 31, 2022

Last Verified

October 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-03-110

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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