A Phase I Trial of Vandetanib (AZD6474) and Selumetinib (AZD6244) for Solid Tumours Including Non Small Cell Lung Cancer (VanSel-1)

Inclusion Criteria: 1. (Dose escalation cohorts) Histologically or cytologically proven solid tumour for which no conventional therapy exists or is declined by the patient 2. (Expansion cohort only) Histologically or cytologically confirmed NSCLC patients only, for which no conventional therapy exists or is declined by the patient. * If only cytologically confirmed, baseline biopsy is mandatory for a patient to be eligible. * For NSCLC patients to be eligible for the expansion cohort they must have received: * One prior line of chemotherapy and/or * Previous platinum based chemotherapy and/or * At least one previous EGFR inhibitor 3. (Expansion cohort only) Measurable disease according to RECIST criteria Version 1.1 in final version of the protocol 4. Life expectancy of at least 12 weeks 5. World Health Organisation (WHO) performance status of 0-1 6. Baseline LVEF \> 50% 7. Haematological and biochemical indices within the ranges shown below. These measurements must be performed within one week (Day -7 to Day -1) before the patient goes on study. Laboratory Test Value required Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 10\^9/L Platelet count ≥ 100 x 10\^9 /L Normal serum calcium (adjusted)\* 2.15-2.55 mmol/L Normal serum magnesium\* 0.60-1.0 mmol/L Normal serum potassium \>4.0 mmol/L Either: Serum bilirubin ≥1.5 x upper limit of normal (ULN) This does not apply to patients with Gilbert's disease. Alanine amino-transferase (ALT) or aspartate amino-transferase (AST) and alkaline phosphatase (ALP) ≤ 2.5 x ULN unless raised due to liver metastases in which case up to 5 x ULN is permissible Either: Calculated creatinine clearance (using the Wright or C\&G formula) \> 50 mL/min Or: Isotope clearance measurement\*\* ≥ 50 mL/min (uncorrected) INR or aPTT \< 1.5 x ULN \*or normal range according to the local laboratory \*\* Isotope clearance result to be used to confirm eligibility if calculated C\&G/Wright method results in GFR of = 50 mL/min. \*\*\* Therapeutic INR values (2.0-3.0) are acceptable to confirm eligibility for patients who are taking concomitant warfarin. 8. 18 years or over 9. Ability to swallow and retain oral medications. 10. Written (signed and dated) informed consent and be capable of co-operating with treatment, and follow-up Exclusion Criteria: 1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous 4 weeks (6 weeks for investigational medicinal products) before treatment. 2. Patients who have been withdrawn from treatment with agents that target EGFR because of unacceptable toxicity (prior treatment with these agents is allowed) and those patients who have had EGFR dose reductions by 50% or more. 3. Expansion cohort only: Prior treatment with any agent that targets MEK or VEGFR 4. Any prior exposure to RAS or RAF inhibitors 5. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 2 toxicities, which in the opinion of the Investigator and the Centre for Drug Development (CDD) should not exclude the patient. 6. Symptomatic brain metastases (patients must be stable for \>3 months post RT treatment) or spinal cord compression. 7. Patients with interstitial lung disease. 8. Pregnant or lactating women are excluded. Female patients with the ability to become pregnant who have a negative serum or urine pregnancy test before enrollment and agree to use two of the following three highly effective forms of combined contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible. 9. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception \[condom plus spermicide\] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate. 10. Major surgery from which the patient has not yet recovered. 11. At high medical risk because of non-malignant systemic disease including active uncontrolled infection. 12. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV). 13. Cardiac conditions as follows: * Clinically significant cardiovascular event within 3 months prior to entry to include: * Myocardial infarction * Angina requiring use of nitrates more than once weekly * Superior vena cava syndrome * Class II/III/IV cardiac disease (New York Heart Association \[NYHA\]) * Presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia. * History of arrhythmia which is symptomatic or requires treatment (CTCAE V4.02), symptomatic or uncontrolled atrial fibrillation despite treatment or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted. * Uncontrolled hypertension (BP \> 160/100 despite optimal therapy) * Prior or current cardiomyopathy * Atrial fibrillation with heart rate \> 100 bpm * QTcB \> or equal to 450 msec on screening ECG (Note: If a patient has a QTcB interval \> or equal to 450 msec on screening ECG, the screen ECG may be repeated twice \[at least 24 hours apart\]. The average QTcB from the three screening ECGs must be \< 450 msec in order for the subject to be eligible for the study.) * History of congenital long QT syndrome * History of Torsade de Pointes (or any concurrent medication with a known risk of inducing Torsades de Pointes.) 14. Concomitant medications that are potent inducers of CYP3A4 function i.e. rifampicin, rifabutin, phenytoin, carbamazepine, Phenobarbital and St John"s Wort. 15. Any other condition which in the Investigator"s opinion would not make the patient a good candidate for the clinical trial (e.g. evidence of severe or uncontrolled systemic disease or concurrent condition or that may affect ability to absorb oral agents). 16. Current malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years or more and are deemed at negligible risk for recurrence, are eligible for the trial. 17. If a participant plans to participate in another interventional clinical study, whilst taking part in this Phase I study. Participation in an observational study would be acceptable. 18. Ophthalmological conditions as follows: 1. Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion. 2. Intraocular pressure (IOP) \> 21 mmHg or uncontrolled glaucoma (irrespective of IOP).