A Phase I Trial of Vandetanib (ZD6474) and Selumetinib (AZD6244)for Solid Tumours Including Non Small Cell Lung Cancer (VanSel-1)
The purpose of this study is to determine whether using two drugs together called vandetanib and selumetinib is effective in the treatment of cancer. The first part of this study will include patients with any solid tumour and the second part of this study will include only patients with non small cell lung cancer. The four main aims of this clinical study are to find out:
- If the two drugs can be given safely to patients when given together.
- The maximum dose that can be given safely to patients.
- More about the potential side effects of the drugs and how they can be managed.
- What happens to vandetanib and selumetinib inside the body.
Non Small Cell Lung Cancer
Drug: Vandetanib, Selumetinib
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Cancer Research UK Phase I Dose Escalation Trial of Oral VEGFR and EGFR Inhibitor, Vandetanib in Combination With the Oral MEK Inhibitor, Selumetinib (VanSel-1) in Solid Tumours (Dose Escalation) and NSCLC (Expansion Cohort).|
- Determining causality of each adverse event to vandetanib or selumetinib and grading severity according to NCI CTCAE Version 4.02 [ Designated as safety issue: Yes ]
- Determining the MTD of the combination of vandetanib and selumetinib [ Designated as safety issue: Yes ]
- During the dose escalation phase: plasma PK profiles [ Designated as safety issue: No ]Determine the plasma PK profiles of vandetanib and selumetinib and their metabolites.
- During the expansion cohort: PFS [ Designated as safety issue: No ]Determine the PFS at 12 weeks by RECIST criteria.
- During the expansion cohort:1 year survival rate [ Designated as safety issue: No ]Determine the 1 year survival rate.
- During the expansion cohort: tumour metabolism [ Designated as safety issue: No ]Assess tumour metabolism using FDG-PET-CT imaging.
|Study Start Date:||December 2011|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Drug: Vandetanib, Selumetinib
- Vandetanib higher (lead in) dose once daily (2 or 4 days) followed by vandetanib steady state dose once daily (10 or 12 days) followed by vandetanib steady state dose once daily in combination with selumetinib once/twice daily (28 days).
- Cycle 1 is 42 days in length.
- Vandetanib steady state once daily in combination with selumetinib once/twice daily(28 days).
- Cycle 2 and subsequent cycles are 28 days in length. From this phase, we will establish what the maximum tolerated dose (MTD) of the combination treatment is, which can safely be given to patients.
- Vandetanib higher dose (lead in) once daily (2 or 4 days) followed by vandetanib steady state dose once daily (10 or 12 days) followed by vandetanib steady state dose once daily in combination with selumetinib once/twice daily (28 days).
- Cycle 1 is 42 days in length.
Dose escalation phase This phase consists of various cohorts, each investigating an increasing dose level of vandetanib and/or selumetinib. Vandetanib steady state dose levels investigated include 100, 200 or 300mg OD. Selumetinib dose levels are 25mg bd, 50mg bd and 75mg bd or 100 and 125mg OD.
All patients in this phase will take the study treatment as follows:
Cycle 2 onwards
Expansion cohort (patients with non small cell lung cancer).
All patients will receive the same dose of combination treatment (the MTD established during dose escalation phase). As follows:
All patients in the expansion cohort will take the study treatment in the same way as follows:
Cycle 2 onwards •o Vandetanib steady state dose once daily in combination with selumetinib once/twice daily (28 days).
o Cycle 2 and subsequent cycles are 28 days in length. Number of cycles: Patients will be allowed to receive 6 cycles of study treatment. If the patient is still benefiting clinically and experiencing no unacceptable toxicity, then the Investigator can make a request to the Sponsor for continuation of treatment.
The purpose of this Phase I study is to establish a safety and toxicity profile of combining two study drugs; vandetanib, a VEGFR (Vascular Endothelial Growth Factor Receptor) and EGFR (Epidermal Growth Factor Receptor) inhibitor, with selumetinib a MEK (Mitogen Activated Kinase)inhibitor.
This is the first time the drugs have been used together. These types of drugs have shown an effect in non small cell lung cancer (NSCLC) therefore the aim is to see if combining these drugs has an increased anti-tumour effect for this group of patients for which treatment options are limited.
The study is in two parts; the dose escalation phase and the expansion cohort.
In the dose escalation phase, 9-50 patients will receive vandetanib and increasing doses of selumetinib to establish a safe dose to recommend for the next stage of the study. Patients with any solid tumour will be eligible.
In the expansion cohort, approximately 30 patients will receive the dose recommended in the previous phase. Only patients with NSCLC will be eligible for this part of the study.
The expansion cohort will look at further evaluating the safety of the drug combination and the anti-tumour activity. Patients in this cohort will be requested to also consent to have additional imaging assessments and optional tumour biopsies.
Study treatment is administered orally; vandetanib tablets once daily and selumetinib capsules twice daily. Cycle 1 is 42 days long. Subsequent cycles are 28 days in length. Patients will receive a total of 6 cycles of the combination treatment. If the patient has not progressed after six cycles, they may be treated for further cycles following approval from the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01586624
|Cambridge Cancer Trials Centre (S4), Box 279, Addenbrooke's Hospital||Recruiting|
|Hills Road, Cambridge, United Kingdom, CB2 0QQ|
|Contact: Simon Pacey, Dr 01223 768435 firstname.lastname@example.org|
|Principal Investigator: Simon Pacey, Dr|
|The Christie NHS Foundation Trust||Recruiting|
|Withington, Manchester, United Kingdom, M20 4BX|
|Contact: Fiona Blackhall, Dr 0161 446 3745 email@example.com|
|Principal Investigator: Fiona Blackhall, Dr|
|Headington, Oxford, United Kingdom, OX3 7LJ|
|Contact: Denis Talbot, Dr 01865 235 315 firstname.lastname@example.org|
|Principal Investigator: Denis Talbot, Dr|
|The Freeman Hospital||Recruiting|
|Newcastle, United Kingdom, NE7 7DN|
|Contact: Alastair Greystoke, Dr 01223768435 Alastair.Greystoke@newcastle.ac.uk|
|Principal Investigator: Alastair Greystoke, Dr|