A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination with Docetaxel, Compared with Placebo in Combination with Docetaxel, in Patients receiving second line treatment for Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB-IV)
- Conditions
- lung cancerNon small cell lung cancer10038666
- Registration Number
- NL-OMON40353
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 19
* Provision of informed consent
* Male and female patients
* Aged at least 18 years
* Histological or cytological confirmation of locally advanced or metastatic non small cell lung cancer
* Prospective confirmation of KRAS mutation negative status as determined using the cobas KRAS mutation Test via an AstraZeneca approved laboratory
* Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
* WHO Performance status 0-1
* At least one evaluable lesion
* Serum creatinin clearance >50 mL/min
* Negative pregnancy test or postmenopausal
* Patients should be able to swallow capsules
- Mixed small cell and non-small cell lung cancer histology;- Received >1 prior anti-cancer drug regimen for advanced or metatstatic NSCLC;- Having received an investigational drug or any other systemic anti-cancer therapy within 30 days of starting treatment or within five half-lives of the compound;- Other concomitant anti-cancer therapy agents except steroids;- Prior treatment with a MEK inhibitor or any docetaxel-containing regimen;- Sympotomatic brain metastases or spinal cord compression. Patients with asymptomatic brain metastasis or treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study are eligible;- Laboratory values as listed below:
* ANC <1.5 x 109/L (1500 per mm3)
* Platelets <100 x 109/L (100.000 per mm3)
* Haemoglobin < 9.0 g/dL
* Serum bilirubin > 1.5 x Upper Limit of Normal
* AST or ALT in patients with no liver metastasis: >2.5 x ULN
* AST or ALT in patients with liver metastasis: >5 x ULN
* AST or ALT > 3.5 x ULN and <5 x ULN in patients with liver metastasis and ALP > 6 x ULN;- Cardiac conditions as follows:
* Uncontrolled hypertension (BP >150/95 mmHg)
* Acute coronary syndrome within 6 months prior to starting treatment
* Angina Canadian Cardiovascular Society grade II-IV
* Symptomatic heart failure
* Prior or current cardiomyopathy
* Baseline LVEF < 55% by echocardiography or MUGA
* Several valvular heart disease
* Atrial fibrilation with a ventricular rate >100 bpm on ECG at rest;* Any evidence of severe uncontrolled systemic disease, active infection, active bleeding diatheses or renal transplant including hepatitis B, C and HIV;* Refractory nausea and vomiting, chronic gastrointestinal diseases or significant bowel resection that would preclude adequate absorption;- Ophthalmologic conditions:
* Current or past history of central serous retinopathy
* Current or past history of retinal vein occlusion
* Intraocular pressure > 21 mmHg or uncontrolled glaucoma
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Progression Free Survival (PFS)</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Overall survival (OS)<br /><br>- Objective Response Rate (ORR)<br /><br>- Duration of Response (DoR)<br /><br>- Change in tumor size<br /><br>- Safety<br /><br>- Tolerability<br /><br>- To explore whether KRAS mutation is predictive of efficacy of selumetinib in<br /><br>combination with docetaxel, compared to docetaxel alone<br /><br>- To assess the effect on non small cell lung cancer symptoms<br /><br>- To assess the effect on health-related quality of life<br /><br>- To investigate the pharmacokinetics of Selumetinib and N-desmethyl<br /><br>Selumetinib when administered in combination with docetaxel.</p><br>