Clinical Trials /

Single-arm Study of Selumetinib in Combination With Docetaxel, in Advanced Gastric Adenocarcinoma Patients With Low/High MEK Signature, RAS Mutation or RAS Amplification as a Second-line Chemotherapy

NCT02448290

Description:

This study is a single-arm, phase II study of selumetinib in combination with docetaxel in patients with advanced gastric adenocarcinoma harboring MEK signature, RAS mutation or amplification as a second line chemotherapy. Selumetinib will be administered orally 75mg twice a day continuously. Docetaxel will be administered as an IV infusion over 1 hour at 60 mg/m2 every 3 week of a 21 days schedule.

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

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Single-arm Study of Selumetinib in Combination With Docetaxel, in Advanced Gastric Adenocarcinoma Patients With Low/High MEK Signature, RAS Mutation or RAS Amplification as a Second-line Chemotherapy
  • Official Title: Phase II, Single-arm Study of Selumetinib in Combination With Docetaxel, in Advanced Gastric Adenocarcinoma Patients With Low/High MEK Signature, RAS Mutation or RAS Amplification as a Second-line Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 2014-04-126
  • NCT ID: NCT02448290

Conditions

  • Gastric Adenocarcinoma

Interventions

DrugSynonymsArms
docetaxel plus selumetinibdocetaxel+selumetinib

Purpose

This study is a single-arm, phase II study of selumetinib in combination with docetaxel in patients with advanced gastric adenocarcinoma harboring MEK signature, RAS mutation or amplification as a second line chemotherapy. Selumetinib will be administered orally 75mg twice a day continuously. Docetaxel will be administered as an IV infusion over 1 hour at 60 mg/m2 every 3 week of a 21 days schedule.

Trial Arms

NameTypeDescriptionInterventions
docetaxel+selumetinibExperimentalSelumetinib 75 mg will be administered orally twice a day with continuous dosing schedule Docetaxel 60 mg/m2 will be administered via intravenous access every 3 weeks.
  • docetaxel plus selumetinib

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
             firstline therapy.

               -  The 1st line regimen must have contained doublet 5-fluoropyrimidine and platinum
                  based regimen.

               -  Relapse within 6 months of completion of adjuvant/neoadjuvant chemotherapy
                  containing doublet 5-fluoropyrimidine and platinum-based regimen could be
                  considered as 1st line therapy.

          4. Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months
             prior to starting the 1st line therapy.

          5. Provision of tumor sample (from either a resection or biopsy)

          6. Patients with MEK signature, RAS mutation or 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)

          7. Patients are willing and able to comply with the protocol for the duration of the
             study including undergoing treatment and scheduled visits and examinations.

          8. ECOG performance status 0-1.

          9. Patients must have a life expectancy ≥ 3 months from proposed first dose date.

         10. 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/L (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

         11. At least one measurable lesion that can be accurately assessed by imaging or physical
             examination at baseline and following up visits.

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

         13. Provision of consent for mandatory biopsy at progression

        Exclusion Criteria:

          1. More than one prior chemotherapy regimen (except for adjuvant/neoadjuvant chemotherapy
             with more than 6 month wash out period) for the treatment of gastric cancer in the
             advanced setting.

          2. Any previous treatment with MEK, RAS or RAF inhibitors

          3. Any previous treatment with docetaxel.

          4. 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.

          5. HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)

          6. Patients unable to swallow orally administered medication.

          7. Treatment with any investigational product during the last 14 days before the
             enrollment (or a longer period depending on the defined characteristics of the agents
             used).

          8. 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.

          9. Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole,
             ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.

         10. With the exception of alopecia, any ongoing toxicities (>CTCAE grade 1) caused by
             previous cancer therapy.

         11. Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks
             before the enrollment.

         12. 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.

         13. 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

         14. Ophthalmological conditions as follows:Intra-ocular pressure >21 mmHg, or uncontrolled
             glaucoma (irrespective of intra-ocular pressure), Current or past history of retinal
             pigment epithelial detachment/central serous retinopathy or or current or past history
             retinal vein occlusion

         15. 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

         16. 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:response rate
Time Frame:24 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:duration of response
Time Frame:24 weeks
Safety Issue:
Description:
Measure:disease control rate
Time Frame:8weeks
Safety Issue:
Description:
Measure:overall survival
Time Frame:up to 100weeks
Safety Issue:
Description:
Measure:progression-free survival
Time Frame:up to 100weeks
Safety Issue:
Description:
Measure:safety assessed by safety( AEs/SAEs)
Time Frame:up to 100weeks
Safety Issue:
Description:The following parameters will be recorded for each ECG: date and time of ECG, heart rate (beats/min), QT (ms), QTcB (ms), sinus rhythm (yes/no), and overall evaluation (normal/abnormal)

Details

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

Trial Keywords

  • gastric adenocarcinoma patients with low/high MEK signature,

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