A phase I and randomised phase II study of docetaxel and RAD001 (Everolimus) in advanced / recurrent or metastatic squamous cell carcinoma of the head and neck

ISRCTN	ISRCTN73814534
DOI	https://doi.org/10.1186/ISRCTN73814534
ClinicalTrials.gov (NCT)	NCT01313390
Protocol serial number	BRD/06/053
Sponsor	University College London (UCL) (UK)
Funders	Novartis (International), Sanofi-Aventis (International)

Submission date: 06/06/2007
Registration date: 20/07/2007
Last edited: 29/11/2011

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

http://www.cancerhelp.org.uk/trials/a-trial-looking-at-docetaxel-and-rad001-for-head-and-neck-cancer-that-has-spread-or-has-come-back-after-treatment

Contact information

Prof Chris Boshoff
Scientific

Wolfson Institute for Biomedical Research
The Cruiciform Building
Gower Street
London
WC1E 6BT
United Kingdom

Email	dora@ctc.ucl.ac.uk

Study information

Primary study design	Interventional
Study design	Phase I: Dose escalation study Phase II: Randomised study of docetaxel (75 mg/m^2) vs docetaxel (75 mg/m^2) + RAD001 (at dose determined in phase I)
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	DORA
Study objectives	To determine the maximum tolerated dose of RAD001 (with docetaxel) in the phase I study and to use this dose in a randomised trial in the phase II setting. As of 17/02/2011 the anticipated end date for this trial has been updated from 01/08/2009 to 01/06/2012.
Ethics approval(s)	South West Research Ethics Committee on 12/03/2008 (ref: 07/H0206/68).
Health condition(s) or problem(s) studied	Advanced / recurrent or metastsatic squamous cell carcinoma of the head and neck.
Intervention	Phase I: RAD001 and docetaxel (75 mg/m^2, intravenous). The starting dose of RAD001 is 10 mg orally and the dose will escalate by 10 mg to a maximum of 50 mg. At least 3 patients will be entered per cohort and if there is no adverse toxicity a further 3 patients are entered at the next dose level. Phase II: Randomised study of docetaxel (75 mg/m^2) vs docetaxel (75 mg/m^2) + RAD001 (at dose determined in Phase I) In both phases, docetaxel will be administered for a maximum of 6 cycles (18 weeks). RAD001 will then continue after chemotherapy has finished (duration depends on each patients condition)
Intervention type	Drug
Phase	Phase I/II
Drug / device / biological / vaccine name(s)	Everolimus, docetaxel
Primary outcome measure(s)	Phase I: 1. To determine the safety and tolerability of the combination of RAD001 and docetaxel 2. To determine the maximum tolerated dose of RAD001 when combined with docetaxel Phase II: To examine the response rates in patients receiving the combination of docetaxel and RAD001 and those receiving docetaxel alone. Scans will be repeated after 2, 4 and 6 cycles. Tumour shrinkage on any scan will count as a response.
Key secondary outcome measure(s)	Phase I: 1. To investigate possible pharmacokinetic interactions between docetaxel and RAD001 2. To investigate the effect of RAD001 on downstream targets of mTOR in tumour Phase II: 1. To examine the time to progression after docetaxel and RAD001 2. To perform a pilot study to attempt to identify predictors of response including evaluation of EGFR family member expression, mutations or amplifications. Also downstream targets of the EGFR pathway including phosphorylation of S6 and phosphorylation of AKT.
Completion date	01/06/2012
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	120
Key inclusion criteria	1. Locally advanced or metastatic squamous cell carcinoma of the head and neck (histologically proven) 2. Estimated life expectancy of at least 12 weeks 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 4. Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST) criteria (NB: For the purposes of this study recurrent disease within a previous radiation field can be considered to be measurable) 5. Aged 18 years or over 6. Patient willing and able to give written informed consent 7. Haematological parameters within a week prior to study entry: - 7.1. Blood cell counts: a. Absolute neutrophils greater than or equal to 1.5 x 10^9/L b. Platelets greater than or equal to 100 x 10^9/L c. Haemoglobin greater than or equal to 10 g/dl 7.2. Renal function: a. Urea and creatinine within normal limits 7.3. Hepatic functions: a. Serum bilirubin within normal limits b. AST or ALT <1.5 x ULN with alkaline phosphatase <2.5 x ULN 8. Patients may have received one line of prior chemotherapy for locally advanced or metastatic disease (but not a taxane) 9. Patients may have received prior radiation therapy for locally advanced or metastatic disease (but must have completed the radiotherapy more than six months before recruitment) 10. Female patients potentially able to child bear should have a negative pregnancy test prior to commencing the study drugs, and agree to use an approved contraceptive method (Intrauterine Device [IUD], birth control pills or barrier device) during and for 3 months after the last dose of the study drugs. All male patients should take adequate contraceptive precautions during and up to 2 months after the last dose of the study drugs
Key exclusion criteria	1. Potentially curable disease 2. Disease relapsed within 6 months of radiotherapy 3. Patients with locally advanced disease for whom radiotherapy is indicated 4. Previous chemotherapy for any cancer, except for head and neck cancer 5. Previous chemotherapy with a taxane 6. Previous therapy with any erbB inhibitors (except Cetuximab given with radiotherapy, as indicated in treatment algorithm) 7. Treatment within the last 4 weeks with any investigational drug 8. The current use of drugs which are known to inhibit CYP3A4 (except dexamethasone), or block P-glycoprotein, including grapefruit juice 9. Evidence of the presence of central nervous system metastases 10. Evidence of uncontrolled infection 11. Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study 12. History of hypersensitivity to docetaxel or any of its excipients 13. Pregnant or breast-feeding
Date of first enrolment	01/08/2007
Date of final enrolment	01/06/2012

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Wolfson Institute for Biomedical Research

London
WC1E 6BT
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan