Locally Advanced or Metastatic NSCL Cancer Stage IIIB IV Clinical Trial
— SELECT-3Official title:
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)
| Verified date | March 2018 |
| Source | AstraZeneca |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 55 |
| Est. completion date | January 4, 2016 |
| Est. primary completion date | January 4, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 99 Years |
| Eligibility |
Inclusion Criteria: - 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 Exclusion Criteria: - 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 |
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Research Site | Glasgow | |
| United Kingdom | Research Site | London | |
| United Kingdom | Research Site | Manchester | |
| United Kingdom | Research Site | Newcastle upon Tyne |
| Lead Sponsor | Collaborator |
|---|---|
| AstraZeneca |
United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib | 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 | The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks | |
| Secondary | Best Objective Response | 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 | Screening, week 6 and week 12 | |
| Secondary | Percentage Change From Baseline at 6 Weeks in Target Lesion Size | The percentage change in the sum of the diameters of target lesions | Week 6 | |
| Secondary | Best Percentage Change From Baseline in Target Lesion Size | 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 | Screening, week 6 and week 12 | |
| Secondary | Objective Response Rate (ORR) | 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 | Up until progression or last evaluable assessment in the absence of progression, up to 9 months | |
| Secondary | AUC (0-tau) | Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau) | Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose | |
| Secondary | Cmax,ss | Maximum plasma concentration at steady state | Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose | |
| Secondary | Tmax,ss | Time to reach maximum plasma concentration at steady state | Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose | |
| Secondary | CL/F | Apparent oral plasma clearance | Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose |