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

Phase 1
18 Years
Open (Enrolling)
Non Small Cell Lung Cancer

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Trial Information

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

As above

Inclusion Criteria:

- 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

- 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

- 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

- 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

Exclusion Criteria:

- 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

- History / evidence of active bleeding diatheses

- History of unstable diabetes

- 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

- Clinical judgement by the investigator that the patient should not participate in the

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

18 months

Safety Issue:


Principal Investigator

Corinne Faivre-Finn, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

The Christie NHS Foundation Trust


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

May 2010

Completion Date:

August 2016

Related Keywords:

  • Non Small Cell Lung Cancer
  • MEK inhibitor
  • thoracic radiotherapy
  • lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms