Head and Neck CancerPhase 1/2DORANCT01313390
Everolimus and Docetaxel in Treating Patients With Recurrent, Locally Advanced, or Metastatic Head and Neck Cancer
A Phase 1/2 study testing docetaxel, everolimus and laboratory biomarker analysis in people with Head and Neck Cancer, run by University College, London at 1 site in United Kingdom.
Trial summary
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- docetaxel, everolimus and laboratory biomarker analysis
- How many people
- 4 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2009to Apr 2011
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed squamous cell carcinoma of the head and neck
- Locally advanced or metastatic disease
- No patients with locally advanced disease for whom radiotherapy is indicated
- Recurrent disease
- Incurable disease
- Measurable disease by RECIST criteria
- Recurrent disease within a prior radiation field can be considered to be measurable
- Patients may have received 1 line of prior chemotherapy (but not a taxane) for locally advanced or metastatic disease
- Patients may have received prior radiation therapy for locally advanced or metastatic disease (but must have completed the radiotherapy > 6 months before recruitment)
- No disease relapsed within 6 months of radiotherapy
- No evidence of central nervous system metastases
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Life expectancy ≥ 12 weeks
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Hemoglobin ≥ 10 g/dL
- Urea and creatinine normal
- Serum bilirubin normal
- AST or ALT ≤ 1.5 times upper limit of normal (ULN)
- Alkaline phosphatase < 2.5 times ULN
- Negative pregnancy test
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 3 months (female) or 2 months (male) after the last dose of the study treatment
- No uncontrolled infection
- No mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study
- No prior malignancy likely to interfere with the patient's ability to comply with treatment and/or follow up
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior chemotherapy for any cancer, except for head and neck cancer
- No prior taxane
- No prior therapy with any erbB inhibitors (except cetuximab given with radiotherapy, as indicated in treatment algorithm)
- More than 6 months since prior radiotherapy for locally advanced or metastatic disease
- At least 4 weeks since prior investigational drug
- No concurrent use of drugs known to inhibit CYP3A4 (except dexamethasone), or block P-glycoprotein, including grapefruit juice
- No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or experimental medications
- No concurrent live vaccines during everolimus therapy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: DORA: A Phase I and Randomized Phase II Study of Docetaxel and RAD001 (Everolimus) in Advanced/Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving everolimus together with docetaxel is more effective than giving docetaxel alone in treating patients with head and neck cancer.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus given together with docetaxel in treating patients with recurrent, locally advanced, or metastatic head and neck cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the safety and tolerability of the combination of everolimus and docetaxel in treating patients with recurrent, locally advanced or metastatic squamous cell carcinoma of the head and neck. (Phase I)
- To determine the maximum-tolerated dose and recommended phase II dose of everolimus when combined with docetaxel in these patients. (Phase I)
- To examine the response rates in patients receiving the combination of docetaxel and everolimus and those receiving docetaxel alone. (Phase II)
Secondary
- To investigate possible pharmacokinetic interactions between docetaxel and everolimus in these patients. (Phase I)
- To investigate the effect of everolimus on downstream targets of mTOR in tumor in these patients. (Phase I)
- To examine the time to progression after docetaxel and everolimus in these patients. (Phase II)
- To perform a pilot study to attempt to identify predictors of response, including evaluation of EGFR family member expression, mutations, or amplifications. (Phase II)
- To attempt to identify downstream targets of the EGFR pathway including phosphorylation of S6 and phosphorylation of AKT. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of everolimus with docetaxel followed by a randomized phase II study.
- Phase I: Patients receive docetaxel IV over 1 hour on day 1 and escalating doses of oral everolimus on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses of therapy, patients may continue to receive everolimus weekly as a single agent until evidence of progressive disease.
- Phase II: Patients are randomized to 1 of 2 treatment arms:
- Arm A: Patients receive docetaxel IV over 1 hour on day 1.Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with progressive disease are eligible to cross over into the everolimus arm at the investigator's discretion.
- Arm B: Patients receive docetaxel as in arm A and oral everolimus (at a dose determined in the phase I portion of the study) on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the completion of combination therapy, patients may continue to receive maintenance everolimus weekly, at the investigator's discretion.
Blood samples are collected for pharmacokinetic monitoring in the phase I study. Tissue samples are collected at baseline and periodically during the study for biomarker and other laboratory analysis.
After completion of study treatment, patients are followed up every 3 months for at least 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
PROJECTED ACCRUAL: Approximately 18 patients will be accrued for phase I and a total of 100 patients will be accrued for phase II of this study.
- Conditions
- Head and Neck Cancer
- Being tested
- docetaxel, everolimus, laboratory biomarker analysis, pharmacological study
- Keywords
- recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx, recurrent verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the lip and oral cavity, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, recurrent verrucous carcinoma of the oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV verrucous carcinoma of the oral cavity, metastatic squamous neck cancer with occult primary squamous cell carcinoma, recurrent metastatic squamous neck cancer with occult primary, recurrent squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Salivary Gland Neoplasms, Tongue Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
docetaxelDrug
everolimusDrug
laboratory biomarker analysisOther
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I)
Safety and tolerability of the combination of everolimus and docetaxel
Response using RECIST criteria (phase II)
Secondary outcomes (5)
Pharmacokinetic profile of docetaxel with and without concurrent everolimus (phase I)
Pharmacokinetic profile of everolimus with and without concurrent docetaxel (phase I)
Time to progression following response (time from treatment start to tumor progression as defined by RECIST criteria) (phase II)
Mutations in EGFR1, AKT, mTOR, ras, or p53 to be tested on paraffin-embedded tissue from the primary or secondary tumor; results to be correlated with outcome (phase II)
Amplifications of EGFR1 and bcl2 expression to be tested by FISH and immunostaining on paraffin-embedded tissue from primary tumor; results to be correlated with outcome (phase II)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2011 (estimated)
- Study startJun 2009
- Primary completionApr 2011
- Study completionApr 2011
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chris Boshoff, Principal investigator, University College London (UCL) Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01313390
- Sponsor's protocol ID
- CDR0000696702
- Other IDs
- CRUK-UCL-06/053, EU-20959, ISRCTN-73814534, EUDRACT-2007-001951-20, CRUK-UCL-CTA-20363/0229/011-00, NOVARTIS-CRUK-UCL-06/053, AVENTIS-CRUK-UCL-06/053
- Acronym
- DORA
- Status last verified
- Dec 2011
- First submitted
- 10 Mar 2011
- Last updated
- 12 Dec 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DORA: A Phase I and Randomized Phase II Study of Docetaxel and RAD001 (Everolimus) in Advanced/Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
- ClinicalTrials.gov ID
- NCT01313390
- Acronym / sponsor ID
- DORA / CDR0000696702
- Conditions
- Head and Neck Cancer
- Keywords
- recurrent squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the hypopharynx, stage IV squamous cell carcinoma of the hypopharynx, stage III squamous cell carcinoma of the larynx, stage III verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, recurrent squamous cell carcinoma of the larynx
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- Jun 2009
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 11 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving everolimus together with docetaxel is more effective than giving docetaxel alone in treating patients with head and neck cancer.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus given together with docetaxel in treating patients with recurrent, locally advanced, or metastatic head and neck cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the safety and tolerability of the combination of everolimus and docetaxel in treating patients with recurrent, locally advanced or metastatic squamous cell carcinoma of the head and neck. (Phase I)
- To determine the maximum-tolerated dose and recommended phase II dose of everolimus when combined with docetaxel in these patients. (Phase I)
- To examine the response rates in patients receiving the combination of docetaxel and everolimus and those receiving docetaxel alone. (Phase II)
Secondary
- To investigate possible pharmacokinetic interactions between docetaxel and everolimus in these patients. (Phase I)
- To investigate the effect of everolimus on downstream targets of mTOR in tumor in these patients. (Phase I)
- To examine the time to progression after docetaxel and everolimus in these patients. (Phase II)
- To perform a pilot study to attempt to identify predictors of response, including evaluation of EGFR family member expression, mutations, or amplifications. (Phase II)
- To attempt to identify downstream targets of the EGFR pathway including phosphorylation of S6 and phosphorylation of AKT. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of everolimus with docetaxel followed by a randomized phase II study.
- Phase I: Patients receive docetaxel IV over 1 hour on day 1 and escalating doses of oral everolimus on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses of therapy, patients may continue to receive everolimus weekly as a single agent until evidence of progressive disease.
- Phase II: Patients are randomized to 1 of 2 treatment arms:
- Arm A: Patients receive docetaxel IV over 1 hour on day 1.Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with progressive disease are eligible to cross over into the everolimus arm at the investigator's discretion.
- Arm B: Patients receive docetaxel as in arm A and oral everolimus (at a dose determined in the phase I portion of the study) on days 1, 8, and 15. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. After the completion of combination therapy, patients may continue to receive maintenance everolimus weekly, at the investigator's discretion.
Blood samples are collected for pharmacokinetic monitoring in the phase I study. Tissue samples are collected at baseline and periodically during the study for biomarker and other laboratory analysis.
After completion of study treatment, patients are followed up every 3 months for at least 1 year.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
PROJECTED ACCRUAL: Approximately 18 patients will be accrued for phase I and a total of 100 patients will be accrued for phase II of this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| docetaxel | Drug | – |
| everolimus | Drug | – |
| laboratory biomarker analysis | Other | – |
| pharmacological study | Other | – |
Primary outcome
Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I)
Safety and tolerability of the combination of everolimus and docetaxel
Response using RECIST criteria (phase II)
5 secondary outcomes
Pharmacokinetic profile of docetaxel with and without concurrent everolimus (phase I)
Pharmacokinetic profile of everolimus with and without concurrent docetaxel (phase I)
Time to progression following response (time from treatment start to tumor progression as defined by RECIST criteria) (phase II)
Mutations in EGFR1, AKT, mTOR, ras, or p53 to be tested on paraffin-embedded tissue from the primary or secondary tumor; results to be correlated with outcome (phase II)
Amplifications of EGFR1 and bcl2 expression to be tested by FISH and immunostaining on paraffin-embedded tissue from primary tumor; results to be correlated with outcome (phase II)
Results and safety
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2011.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Boshoff principal investigator
University College London (UCL) Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing docetaxel, everolimus and laboratory biomarker analysis in people with Head and Neck Cancer, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2011.