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 number NCT01313390
Secondary identifying numbers BRD/06/053
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

Study designPhase 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 designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific title
Study acronymDORA
Study objectivesTo 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) studiedAdvanced / recurrent or metastsatic squamous cell carcinoma of the head and neck.
InterventionPhase 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 patient’s condition)
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase I/II
Drug / device / biological / vaccine name(s)Everolimus, docetaxel
Primary outcome measurePhase 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 measuresPhase 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 study start date01/08/2007
Completion date01/06/2012
Reason abandoned (if study stopped)Participant recruitment issue

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants120 (As of 13/04/2011 this trial has closed as it failed to reach its participant target)
Key inclusion criteria1. 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 criteria1. 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 enrolment01/08/2007
Date of final enrolment01/06/2012

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

Wolfson Institute for Biomedical Research
London
WC1E 6BT
United Kingdom

Sponsor information

University College London (UCL) (UK)
University/education

Joint University College London Hospital (UCLH) & UCL Biomedical Research Unit
1st Floor
Maple House
149 Tottenham Court Road
London
W1P 9LL
England
United Kingdom

ROR logo "ROR" https://ror.org/02jx3x895

Funders

Funder type

Industry

Novartis (International)
Government organisation / For-profit companies (industry)
Alternative name(s)
Novartis AG, Novartis International AG
Location
Switzerland
Sanofi-Aventis (International)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan