Study of TARCEVA (Erlotinib) as Adjuvant Treatment for Locally Advanced Head and Neck Squamous Cell Carcinoma
Status:
Completed
Trial end date:
2014-09-01
Target enrollment:
Participant gender:
Summary
This trial was originally designed and powered to compare biomarker modulation in the
neo-adjuvant setting (erlotinib versus erlotinib plus sulindac versus placebo) with clinical
response to erlotinib in the adjuvant setting. Since implementing the trial in late 2005, The
investigators have encountered significant obstacles to implementing the adjuvant therapy
phase of the trial.
- Barriers included:
1. disease recurrence
2. patient refusal to take the agent
3. patient refusal to travel to Pittsburgh for clinical evaluations.
Given the institutional challenges to implement and complete the adjuvant portion, the
investigators have decided to change the primary endpoint to a biomarker modulation endpoint.
To achieve this goal, the investigators determined that they needed 39 paired tissue
specimens (see statistical justification below).
The central hypothesis to be tested in this study is that persistent activation of parallel
and/or downstream pathways contributes to tumor progression in the setting of EGFR blockade.
While not all head and neck squamous cell carcinoma (HNSCC) patients will respond to EGFR
targeting, the optimal strategy to identify those subjects whose tumors are sensitive to EGFR
inhibition remains unknown.
The primary objective is centered around the concept of tumor biomarkers which may be
modulated by EGFR and Cox-2 inhibitors and may serve as future therapeutic targets for
therapy. To this end patients on this trial will be randomly assigned to one of three arms to
receive either Tarceva, Tarceva plus sulindac, or a placebo in the 2 week pre-operative
period. A panel of biomarkers will be obtained by biopsy prior to pre-operative therapy and
again at surgery. Biomarkers will be examined for modulation in the 2-week pre-operative
period, for group differences, for treatment effects and for further understanding of protein
signaling pathways.
Sample size for the primary objective
Modification of Statistical Design:
The primary endpoint is the difference between pre (biopsy) and post (surgery). There are 3
hypotheses of interest: (1) placebo vs erlotinib alone, (2) placebo versus erlotinib plus
sulindac, and (3) erlotinib vs erlotinib + sulindac. With a randomization in a 3:5:5 ratio,
we have 88% power, alpha = .01 for an omnibus test to show between-group differences of 1 log
exist. This requires 39 patients. Basically, 39 patients will provide the ability to detect a
one log difference between any 2 of the 3 groups in pre-post change.