MEK Inhibitor and Thoracic Radiotherapy Trial (MEKRT)
Two thirds of non small cell lung cancer patients present with locally advanced tumours (stage III) or metastatic disease (stage IV) and radiotherapy plays a major role in their treatment. Treatment (radiotherapy and chemotherapy) can be given with curative intent to selected patients with locally advanced, stage III disease. Patients with stage III tumours associated with a pleural effusion, and patients who present with advanced, metastatic disease (stage IV) are treated palliatively with no prospect of cure. In the latter, radiotherapy (RT) is offered with the aim of improving symptoms, achieving tumour control and optimising quality of life. It is generally believed that a plateau has been reached for combination of chemotherapy with radiotherapy lung cancer. There is a strong rationale for combining molecular targeted agents with irradiation. AZD6244 is a potent, selective, uncompetitive inhibitor of MEK that has been tested in early phase clinical trials either alone or in combination with chemotherapy in a variety of cancers including lung cancer. Preclinical studies have shown that AZD6244 enhances the effect of radiation. AZD6244 has not yet been combined with radiotherapy in clinical trials. In this study, a maximum of 18 patients will be allocated to one of 3 doses of AZD6244 in combination with a standard dose of RT in a Phase 1 dose escalation/ de-escalation design to determine the recommended dose for Phase 2 trials (RP2D). An expanded cohort of 15 patients will be treated at the RP2D to obtain additional safety and preliminary response data. Patients will undergo 3 FLT positron emission tomogram (PET) scans, the first scan before treatment, second scan during AZD6244 treatment and third scan during RT. All patients will also have tissue/blood samples collected for biomarkers. Biomarkers and FLTPET imaging will be examined to obtain information that may predict for response, resistance or toxicity to radiation and AZD6244.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Trial of the MEK Inhibitor AZD6244 in Combination With Thoracic Radiotherapy in Non-small Cell Lung Cancer|
- To determine the recommended phase II dose (RP2D) of AZD6244 in combination with thoracic radiotherapy (RT) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]Recommended Phase II Dose (RP2D) - The RP2D will be the dose level at which < 2/6 patients experience dose limiting toxicity (DLT) during thoracic radiotherapy and for 12 weeks after completion of thoracic radiotherapy during the dose escalation phase. The RP2D will be further evaluated for safety in the expanded cohort.
- Secondary objectives : Safety profile of AZD6244 in combination with thoracic RT Dose delivery of AZD6244 in combination with thoracic RT Response to AZD6244 in combination with thoracic RT [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Safety profile of AZD6244 in combination with thoracic RT. Dose delivery of AZD6244 in combination with thoracic RT. Response to AZD6244 in combination with thoracic RT
|Study Start Date:||May 2010|
|Estimated Study Completion Date:||August 2016|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: AZD6244 & Thoracic Radiotherapy
AZD6244 in combination with thoracic radiotherapy (RT)- the aim is to determine the recommended phase II dose (RP2D).
MEK inhibitor AZD6244 (Selumentinib) in combination with thoracic radiotherapy
Other Name: Selumetinib
|Contact: Sally Falk||0044 161 918 firstname.lastname@example.org|
|Contact: Kate Haslett||0044 161 446 email@example.com|
|The Christie NHS Foundation Trust||Recruiting|
|Manchester, Greater Manchester, United Kingdom, M20 4BX|
|Contact: Sally Falk 0044 161 918 7101 firstname.lastname@example.org|
|Contact: Kate Haslett 0044 161 446 8273 email@example.com|
|Principal Investigator: Corinne Faivre-Finn, MD, PhD|
|Principal Investigator:||Corinne Faivre-Finn, MD, PhD||The Christie NHS Foundation Trust|