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

This study has been terminated.
(Lack of recruitment)
Sponsor:
Information provided by (Responsible Party):
University College, London
ClinicalTrials.gov Identifier:
NCT01313390
First received: March 10, 2011
Last updated: December 9, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: docetaxel
Drug: everolimus
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University College, London:

Primary Outcome Measures:
  • Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I) [ Designated as safety issue: No ]
  • Safety and tolerability of the combination of everolimus and docetaxel [ Designated as safety issue: Yes ]
  • Response using RECIST criteria (phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic profile of docetaxel with and without concurrent everolimus (phase I) [ Designated as safety issue: No ]
  • Pharmacokinetic profile of everolimus with and without concurrent docetaxel (phase I) [ Designated as safety issue: No ]
  • Time to progression following response (time from treatment start to tumor progression as defined by RECIST criteria) (phase II) [ Designated as safety issue: No ]
  • 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) [ Designated as safety issue: No ]
  • 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) [ Designated as safety issue: No ]

Enrollment: 4
Study Start Date: June 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01313390

Locations
United Kingdom
UCL Cancer Institute
London, England, United Kingdom, WC1E 6DD
Sponsors and Collaborators
University College, London
Investigators
Principal Investigator: Chris Boshoff University College London (UCL) Cancer Institute
  More Information

No publications provided

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01313390     History of Changes
Other Study ID Numbers: CDR0000696702, 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
Study First Received: March 10, 2011
Last Updated: December 9, 2011
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University College, London:
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

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Everolimus
Sirolimus
Docetaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 22, 2014