Dose escalation trial of oral Vascular Endothelial Growth Factor Receptor (VEGFR) and Epidermal Growth Factor Receptor (EGFR) inhibitor, Vandetanib in combination with the oral Mitogen Activated Kinase (MEK) inhibitor, Selumetinib (VanSel-1) in solid tumours (dose escalation) and NSCLC (expansion cohort)
- Conditions
- Topic: National Cancer Research NetworkSubtopic: Lung CancerDisease: Lung (non-small cell)CancerMalignant neoplasm of bronchus and lung
- Registration Number
- ISRCTN69481429
- Lead Sponsor
- Cancer Research UK (CRUK) (UK)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 58
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 Non-small cell lung cancer (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:
2.1. One prior line of chemotherapy
2.2. Previous platinum based chemotherapy
Also eligible are those patients who:
2.3. Are erlotinib resistant
2.4. Are untreated with erlotinib
2.5. Have been treated with docetaxel
3. (Expansion cohort only) Measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria Version 1.0
4. Life expectancy of at least 12 weeks
5. World Health Organisation (WHO) performance status of 0-1
6. Baseline left ventricular ejection fraction (LVEF) > or = 50%
7. Haematological and biochemical indices as follows:
7.1. Haemoglobin > or = 9.0g/dL
7.2. Absolute neutrophil count ?> or = 1.5 x 10^9/L
7.3. Platelet count > or = 100 x10^9/L
7.4. Normal serum calcium (adjusted) 2.15-2.55 mmol/L
7.5. Normal serum magnesium 0.60-1.0 mmol/L
7.6. Normal serum potassium ?> or = 4.0mmol/L
7.7. Either: Serum bilirubin ?< or = 1.5 x upper limit of normal (ULN)
This does not apply to patients with Gilbert?s disease or
7.8. Alanine amino-transferase (ALT) or aspartate amino-transferase (AST) and alkaline phosphatase (ALP) ?< or = 2.5 x ULN unless raised due to liver metastases in which case up to 5 x ULN is permissible
7.9. Either: Calculated creatinine clearance (using the Wright formula) > or = 50mL/min. Isotope clearance measurement > or = 50mL/min(uncorrected)
7.10. International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) < 1.5 x ULN
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.; Target Gender: Male & Female ; Lower Age Limit 18 years
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
3. 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 1 toxicities, which in the opinion of the Investigator and the Drug Development Office (DDO) 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 enrolment and agree to use two of three highly effective forms of combined contraception 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 during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception 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:
13.1. Clinically significant cardiovascular event within 3 months prior to entry to include:
13.1.1. Myocardial infarction
13.1.2. Angina requiring use of nitrates more than once weekly
13.1.3. Superior vena cava syndrome
13.1.4. Class II/III/IV cardiac disease (New York Heart Association [NYHA])
13.1.5. Presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
13.1.6. History of arrhythmia which is symptomatic or requires treatment[Common Terminology Criteria for Adverse Events v3.0 (CTCAE 3)], symptomatic or uncontrolled atrial fibrillation despite treatment or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication are permitted.
13.2. Uncontrolled hypertension (BP > 160/100 despite optimal therapy)
13.3. Prior or current cardiomyopathy
13.4. Atrial fibrillation with heart rate >100 bpm
13.5. QTcB > 450 msec on screening electrocardiogram (ECG)
13.6. History of congenital long QT syndrome
13.7. History of Torsade de Pointes (or any concurrent medication with a known risk of inducing Torsades de Pointes.
1
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Identification of toxicity and establish safety profile; Timepoint(s): Throughout study
- Secondary Outcome Measures
Name Time Method Determine maximum tolerated dose for patients and recommend Phase II dose; Timepoint(s): During and end of study