Assess Safety & Efficacy of Selumetinib When Given in Combination With Standard First Line Treatment for Advanced Non-small Cell Lung Cancer
- Conditions
- Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV
- Interventions
- Registration Number
- NCT01809210
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a Phase I, open label multicentre study of selumetinib administered orally in combination with first line chemotherapy regimens to patients with advanced/metastatic NSCLC. The study has been designed to allow an investigation of the optimal dose of selumetinib in combination with various standard first line double-platinum chemotherapy regimens. Initial assessment will be based on tolerability of selumetinib in combination with one or more selected regimens that are considered to be tolerated also being assessed for preliminary evidence of activity.
This study is a dose finding and optional cohort expansion; In addition all patients will be assessed for anti-cancer efficacy of the combination of selumetinib and chemotherapy.
- Detailed Description
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination with First Line Chemotherapy Regimens in Patients with Non-Small Cell Lung Cancer (NSCLC)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
- Provision of signed, written and dated consent prior to any study specific procedures
- Male or female, aged 18 years or older
- Histological or cytological confirmation of locally advanced or metastatic NSCLC (IIIB-IV)
- Female patients must not be breast-feeding and have a negative pregnancy test prior to start of dosing or must have evidence of non-child-bearing potential
- Patients must be eligible to receive treatment with the platinum doublet combination with which selumetinib is being combined and in accordance with the local product information
- Prior chemotherapy or other systemic anti-cancer treatment for advanced NSCLC.
- Prior surgery or radiotherapy within 6 months or palliative radiotherapy within 4 weeks of start of study treatment.
- Female patients who are breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
- Another primary malignancy within 5 years of starting study treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ.
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, active bleeding diatheses, renal transplant, or active infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Selumetinib+standard chemotherapy selumetinib Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin Selumetinib+standard chemotherapy carboplatin Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin Selumetinib+standard chemotherapy gemcitabine Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin Selumetinib+standard chemotherapy cisplatin Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin Selumetinib+standard chemotherapy pemetrexed Selumetinib plus gemcitabine; or pemetrexed and cisplatin or carboplatin
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting
- Secondary Outcome Measures
Name Time Method CL/F Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose Apparent oral plasma clearance
Best Objective Response Screening, week 6 and week 12 The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), \>=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of \>=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10mm
Percentage Change From Baseline at 6 Weeks in Target Lesion Size Week 6 The percentage change in the sum of the diameters of target lesions
Best Percentage Change From Baseline in Target Lesion Size Screening, week 6 and week 12 The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions
Tmax,ss Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose Time to reach maximum plasma concentration at steady state
Objective Response Rate (ORR) Up until progression or last evaluable assessment in the absence of progression, up to 9 months The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10mm; Objective Response Rate (ORR) = CR + PR
AUC (0-tau) Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau)
Cmax,ss Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose Maximum plasma concentration at steady state
Trial Locations
- Locations (1)
Research Site
🇬🇧Newcastle upon Tyne, United Kingdom