Everolimus and Docetaxel in Treating Patients With Recurrent, Locally Advanced, or Metastatic Head and Neck Cancer (DORA)
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.
Head and Neck Cancer
Other: laboratory biomarker analysis
Other: pharmacological study
|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|
- 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 ]
- 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 ]
|Study Start Date:||June 2009|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
- 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)
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01313390
|UCL Cancer Institute|
|London, England, United Kingdom, WC1E 6DD|
|Principal Investigator:||Chris Boshoff||University College London (UCL) Cancer Institute|