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Non Small Cell Lung CancerPhase 1MEKRTNCT01146756

MEK Inhibitor and Thoracic Radiotherapy Trial

A Phase 1 study testing AZD6244 in people with Non Small Cell Lung Cancer, run by The Christie NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
AZD6244
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited Kingdom
Study dates
4 Jun 2010to 8 Feb 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed NSCLC either inoperable, stage III NSCLC or stage IV NSCLC with dominant chest symptoms.
  • Patient age ≥18
  • Willingness and able to comply with treatment, tests and attend the required follow-up
  • Prior chemotherapy is permitted provided the interval between day 8 of the last cycle of chemotherapy and day 1 of AZD6244 dosing is ≥2 weeks
  • No prior radiotherapy or investigational agents
  • Life expectancy estimated to be greater than 3 months
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  • Performance status(ECOG) 0 or 1
  • MRC dyspnoea score <3
  • Patient considered able to tolerate radical radiotherapy
  • FEV1 >40% of predicted and DLCO (transfer factor for carbon monoxide) >40% of predicted
  • Disease which can be encompassed within a radical radiotherapy treatment volume(V20 ≤35% and maximum cord dose 48Gy) on the radiotherapy planning scan
  • Left ventricular ejection fraction >50% on baseline echocardiogram
  • Adequate renal function - defined by GFR >50 ml/min (calculated Cockcroft and Gault) or by isotope GFR.
  • Adequate bone marrow reserve: white cell count >3 x 109/l, absolute neutrophil count >1.5 x 109/l, haemoglobin >10.0 g/dl and platelet count >100 x 109/l (Blood transfusion permitted to achieve Hb >10g/dl)
  • AST/ALT < 2.5 ULN and bilirubin <1.5 ULN
  • Group D (expanded cohort) only: diameter of the primary tumour should be > 2 cm

Who cannot join

  • Mixed non-small cell and small cell tumours
  • Other previous or current malignant disease likely to interfere with protocol treatment or comparisons
  • Lack of recovery from prior chemotherapy toxicity to grade ≤2 except alopecia d)Refractory nausea and vomiting, chronic gastrointestinal diseases (eg, inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption of AZD6244
  • Presence of clinically significant fluid accumulations in third spaces which cannot be adequately controlled by drainage or other procedures prior to inclusion in the study.
  • History / evidence of active bleeding diatheses
  • History of unstable diabetes
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  • History of interstitial pneumonitis
  • Arterial hypertension defined as SBP≥ 160 or DBP ≥100 (antihypertensive medication to achieve these parameters are permissible)
  • Myocardial infarction, or unstable or uncontrolled angina, congestive heart failure (NYHA > class II) within 1 year of enrollment
  • Active infection on day of enrollment
  • Uncontrolled hypercalcemia >3.0 or symptomatic
  • History of hypersensitivity to active or inactive excipients of AZD6244
  • Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) which would prevent administration of study treatment
  • Known and symptomatic brain metastases. Brain imaging is not mandatory if patient is asymptomatic.
  • Clinical judgement by the investigator that the patient should not participate in the study
  • Patients of reproductive potential who are unable to comply with effective contraception if sexually active during the study and for a period of at least 90 days (men) or 6 months after treatment (women)
  • Women who are breastfeeding

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • The Christie NHS Foundation Trust

    Manchester, Greater Manchester, M20 4BX

Other trials in United Kingdom

About this study

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

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.

Read the detailed description

As above

Being tested
AZD6244
Keywords
MEK inhibitor, thoracic radiotherapy, lung cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD6244Drug

    Also called Selumetinib

    MEK inhibitor AZD6244 (Selumentinib) in combination with thoracic radiotherapy

Study groups in NCT01146756
Study groupRoleWhat they receive
AZD6244 & Thoracic RadiotherapyExperimentalAZD6244 in combination with thoracic radiotherapy (RT)- the aim is to determine the recommended phase II dose (RP2D).
Receives: Drug: AZD6244

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the recommended phase II dose (RP2D) of AZD6244 in combination with thoracic radiotherapy (RT)

    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.

    Measured: 18 months

Secondary outcomes (1)

  1. 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

    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

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2010 (estimated)
  2. Study start4 Jun 2010
  3. Primary completion8 Feb 2017
  4. Study completion8 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01146756
Sponsor's protocol ID
09_DOG07_104
Acronym
MEKRT
Status last verified
Feb 2023
First submitted
17 Jun 2010
Last updated
15 Feb 2023
Results posted
No
Data monitoring committee
No

Publications

  • Haslett K, Koh P, Hudson A, Ryder WD, Falk S, Mullan D, Taylor B, Califano R, Blackhall F, Faivre-Finn C. Phase I trial of the MEK inhibitor selumetinib in combination with thoracic radiotherapy in non-small cell lung cancer. Clin Transl Radiat Oncol. 2021 Feb 25;28:24-31. doi: 10.1016/j.ctro.2021.02.008. eCollection 2021 May.

    PubMed 33748440

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD6244 in people with Non Small Cell Lung Cancer, run by The Christie NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the recommended phase II dose (RP2D) of AZD6244 in combination with thoracic radiotherapy (RT) (time frame: 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01146756, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.

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