Contact information
Type
Scientific
Primary contact
Prof Chris Boshoff
ORCID ID
Contact details
Wolfson Institute for Biomedical Research
The Cruiciform Building
Gower Street
London
WC1E 6BT
United Kingdom
dora@ctc.ucl.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT01313390
Protocol/serial number
BRD/06/053
Study information
Scientific title
Acronym
DORA
Study hypothesis
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
South West Research Ethics Committee on 12/03/2008 (ref: 07/H0206/68).
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)
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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 names
Everolimus, docetaxel
Primary outcome measures
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.
Secondary outcome measures
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.
Overall trial start date
01/08/2007
Overall trial end date
01/06/2012
Reason abandoned
Participant recruitment issue
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
120 (As of 13/04/2011 this trial has closed as it failed to reach its participant target)
Participant 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
Recruitment start date
01/08/2007
Recruitment end date
01/06/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Wolfson Institute for Biomedical Research
London
WC1E 6BT
United Kingdom
Funders
Funder type
Industry
Funder name
Novartis (International)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
Switzerland
Funder name
Sanofi-Aventis (International)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary