Clinical Trials /

Study of Vismodegib in Advanced Gastric Adenocarcinoma Patients With SMO Overexpression

NCT03052478

Description:

There is no accepted standard therapy for patients with advanced gastric cancer who have progressed during or after second-line therapy. The role of 3rd line treatment in advanced gastric cancer has not been proven. As a novel target of gastric cancer, SMO overexpression is chosen in this study, and the investigators plan this study to evaluate the efficacy and safety of vismodegib in gastric cancer. The doses of vismodegib are based on trials of basal cell carcinoma.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Vismodegib in Advanced Gastric Adenocarcinoma Patients With SMO Overexpression
  • Official Title: Phase II, Single-arm Study of Vismodegib in Advanced Gastric Adenocarcinoma Patients With SMO Overexpression

Clinical Trial IDs

  • ORG STUDY ID: 2016-08-130
  • NCT ID: NCT03052478

Conditions

  • Stomach Neoplasms

Interventions

DrugSynonymsArms
Vismodegib 150 mgvismodegib arm

Purpose

There is no accepted standard therapy for patients with advanced gastric cancer who have progressed during or after second-line therapy. The role of 3rd line treatment in advanced gastric cancer has not been proven. As a novel target of gastric cancer, SMO overexpression is chosen in this study, and the investigators plan this study to evaluate the efficacy and safety of vismodegib in gastric cancer. The doses of vismodegib are based on trials of basal cell carcinoma.

Trial Arms

NameTypeDescriptionInterventions
vismodegib armExperimental. Vismodegib 150 mg will be administered orally once a day for 21 days as one cycle.
  • Vismodegib 150 mg

Eligibility 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
             1st line or 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.

               -  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 SMO overexpression by IHC

          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. Negative urine or serum pregnancy test within 28 days of study treatment, confirmed
             prior to treatment on day 1. for women of childbearing potential.

         11. Provision of consent for mandatory biopsy at progression (fresh frozen will be
             mandatory if clinically feasible)

         12. Provision of archival or fresh tissue sample at baseline (fresh frozen will be
             mandatory if clinically feasible)

        Exclusion Criteria:

        Patients will be excluded from the study if they meet any of the following 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 Hedgehog pathway inhibitor

          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. 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: 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) (HBV carrier is allowed)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) by RECIST 1.1
Time Frame:6 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Samsung Medical Center

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