Trial Information

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

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.