NCT01146756: MEKRT

MEK Inhibitor and Thoracic Radiotherapy Trial

Completed Phase 1 Last updated 15 February 2023

What this trial tests

Phase 1 trial testing AZD6244 in Non Small Cell Lung Cancer in 21 participants. Completed in 8 February 2017.

Timeline

4 June 2010

Primary endpoint
8 February 2017

8 February 2017

Quick facts

Lead sponsor	The Christie NHS Foundation Trust
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	21
Start date	4 June 2010
Primary completion	8 February 2017
Estimated completion	8 February 2017
Sites	1 location across United Kingdom

Drugs / interventions tested

• AZD6244 — full drug profile →

Conditions studied

• Non Small Cell Lung Cancer — all drugs for Non Small Cell Lung Cancer →

Sponsor

The Christie NHS Foundation Trust

Who can join

18 and older, any sex, with Non Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. A phase II evaluation of selumetinib (AZD6244, ARRY-142886), a selective MEK-1/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology/Gynecologic Oncology Group study.
   Coleman RL, Sill MW, Thaker PH, Bender DP, et al · · 2015 · cited 63× · PMID 25887099 · DOI 10.1016/j.ygyno.2015.04.005
2. Small molecule drugs with immunomodulatory effects in cancer.
   Murphy AG, Zheng L. · · 2015 · cited 27× · PMID 26110550 · DOI 10.1080/21645515.2015.1057363
3. KRAS mutant NSCLC, a new opportunity for the synthetic lethality therapeutic approach.
   de Castro Carpeño J, Belda-Iniesta C. · · 2013 · cited 15× · PMID 25806225 · DOI 10.3978/j.issn.2218-6751.2013.02.07
4. Targeting MEK for the treatment of non-small-cell lung cancer.
   Goldman JW, Garon EB. · · 2012 · cited 10× · PMID 23160324 · DOI 10.1097/jto.0b013e31826df0bc
5. Phase I trial of the MEK inhibitor selumetinib in combination with thoracic radiotherapy in non-small cell lung cancer.
   Haslett K, Koh P, Hudson A, Ryder WD, et al · · 2021 · cited 5× · PMID 33748440 · DOI 10.1016/j.ctro.2021.02.008
6. Recent advances progress of targeted drugs combined with radiotherapy for advanced non-small cell lung cancer: a review.
   Xu J, Wang Z. · · 2023 · cited 1× · PMID 38115908 · DOI 10.3389/fonc.2023.1285593