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