NCT01146756

MEK Inhibitor and Thoracic Radiotherapy Trial

Phase I Trial of the MEK Inhibitor AZD6244 in Combination With Thoracic Radiotherapy in Non-small Cell Lung Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: The Christie NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

As above

Conditions

• Non Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	AZD6244	MEK inhibitor AZD6244 (Selumentinib) in combination with thoracic radiotherapy

Timeline

• Start date: 2010-06-04
• Primary completion: 2017-02-08
• Completion: 2017-02-08
• First posted: 2010-06-22
• Last updated: 2023-02-15

Locations

1 site across 1 country: United Kingdom