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 | Completed Phase 2

• 1 other identifier: 2014-04-126
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastric Adenocarcinoma

Keywords

gastric adenocarcinoma patients with low/high MEK signature,

Outcome Measures

Primary Outcomes (1)

• response rate

  24 weeks

Secondary Outcomes (5)

• duration of response

  24 weeks

• disease control rate

  8weeks

• overall survival

  up to 100weeks

• progression-free survival

  up to 100weeks

• safety assessed by safety( AEs/SAEs)

  up to 100weeks

Study Arms (1)

docetaxel+selumetinib

EXPERIMENTAL

Selumetinib 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.

Drug: docetaxel plus selumetinib

Interventions

docetaxel plus selumetinib DRUG

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.

docetaxel+selumetinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of fully informed consent prior to any study specific procedures.
• Patients must be ≥20 years of age.
• 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.
• Previous adjuvant/neoadjuvant chemotherapy is allowed, if completed more than 6 months prior to starting the 1st line therapy.
• Provision of tumor sample (from either a resection or biopsy)
• 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)
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• ECOG performance status 0-1.
• Patients must have a life expectancy ≥ 3 months from proposed first dose date.
• 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

You may not qualify if:

• 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.
• Any previous treatment with MEK, RAS or RAF inhibitors
• Any previous treatment with docetaxel.
• 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.
• HER2 positive patients (defined by HER2 3+ by immunohistochemistry or HER2 SISH +)
• Patients unable to swallow orally administered medication.
• 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).
• 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.
• Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
• With the exception of alopecia, any ongoing toxicities (\>CTCAE grade 1) caused by previous cancer therapy.
• Intestinal obstruction or CTCAE grade 3 or grade 4 upper GI bleeding within 4 weeks before the enrollment.
• 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.
• 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
• 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
• 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

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical center

Seoul, 135-710, South Korea

Location

MeSH Terms

Interventions

Docetaxel; AZD 6244

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jeeyun Lee, MD, PhD

  Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center,

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center,

Study Record Dates

• First Submitted: January 15, 2015
• First Posted: May 19, 2015
• Study Start: November 12, 2014
• Primary Completion: May 17, 2018
• Study Completion: May 17, 2018
• Last Updated: May 20, 2019

Record last verified: 2019-05

Locations

KR (1)