search
Back to results

Everolimus and Docetaxel in Treating Patients With Recurrent, Locally Advanced, or Metastatic Head and Neck Cancer (DORA)

Primary Purpose

Head and Neck Cancer

Status
Terminated
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
docetaxel
everolimus
laboratory biomarker analysis
pharmacological study
Sponsored by
University College, London
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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, recurrent squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, stage III squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent salivary gland cancer, salivary gland squamous cell carcinoma, stage III salivary gland cancer, stage IV salivary gland cancer, tongue cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCL Cancer Institute

Outcomes

Primary Outcome Measures

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 Outcome Measures

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)

Full Information

First Posted
March 10, 2011
Last Updated
December 9, 2011
Sponsor
University College, London
search

1. Study Identification

Unique Protocol Identification Number
NCT01313390
Brief Title
Everolimus and Docetaxel in Treating Patients With Recurrent, Locally Advanced, or Metastatic Head and Neck Cancer
Acronym
DORA
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Terminated
Why Stopped
Lack of recruitment
Study Start Date
June 2009 (undefined)
Primary Completion Date
April 2011 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, 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, recurrent squamous cell carcinoma of the oropharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity, stage III squamous cell carcinoma of the paranasal sinus and nasal cavity, stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity, recurrent salivary gland cancer, salivary gland squamous cell carcinoma, stage III salivary gland cancer, stage IV salivary gland cancer, tongue cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
docetaxel
Intervention Type
Drug
Intervention Name(s)
everolimus
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I)
Title
Safety and tolerability of the combination of everolimus and docetaxel
Title
Response using RECIST criteria (phase II)
Secondary Outcome Measure Information:
Title
Pharmacokinetic profile of docetaxel with and without concurrent everolimus (phase I)
Title
Pharmacokinetic profile of everolimus with and without concurrent docetaxel (phase I)
Title
Time to progression following response (time from treatment start to tumor progression as defined by RECIST criteria) (phase II)
Title
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)
Title
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chris Boshoff
Organizational Affiliation
University College London (UCL) Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCL Cancer Institute
City
London
State/Province
England
ZIP/Postal Code
WC1E 6DD
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Everolimus and Docetaxel in Treating Patients With Recurrent, Locally Advanced, or Metastatic Head and Neck Cancer

We'll reach out to this number within 24 hrs