| General information |
| Database: | DB00389 |
| Objective: | The EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. They conducted a randomized, doubleblind, placebocontrolled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo. |
| Authors: | Gross ND, et al |
| Title: | Erlotinib, erlotinibsulindac versus placebo: a randomized, doubleblind, placebocontrolled window trial in operable head and neck cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 24727329 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | erlotinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | erlotinibsulindac |
| Study Type: | randomized, doubleblind, placebocontrolled window trial |
| Key Patients Feature: | histologically confirmed, previously untreated HNSCC (Stage IIIVA) of the oral cavity, oropharynx, hypopharynx, or larynx, as defined by the American Joint Committee on Cancer Staging Handbook, 6thedition; planned complete resection of the primary tumor; age more than and equal to 18 years; EasternCooperative Oncology Group performance status 01; adequate hematologic, hepatic andrenal function. |
| Biomarker: | 25 candidate protein biomarkers, including 21empirically selected from preclinical signaling models and 4 from mass spectrometry (MS) discovery. |
| Biomark Analysis: | Ki67 was significantly decreased by erlotinib or erlotinibsulindac (omnibus comparison, twosided KruskalWallis, P = 0.04). Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib groups (erlotinibsulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P = 0.027). There was a significant trend in ordering of Ki67 reduction: erlotinibsulindac > erlotinib > placebo (twosided exact JonckheereTerpstra, P = 0.0185). Low baseline pSrc correlated with greater Ki67 reduction (R(2) = 0.312, P = 0.024). |
| Control Group Info: | A:erlotinib B:erlotinibsulindac B: placebo |
| Treatment Info: | Patients with untreated, operable stage IIIVb HNSCC were randomized 5:5:3 to erlotinib, erlotinibsulindac, or placebo. Tumor specimens were collected before and after seven to 14 days of treatment. |
| Primary End Point: | change in Ki67 proliferation index. |
| Secondary End Point: | 25 candidate protein biomarkers |
| Patients Number: | 47 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | NA |
| Conclusions: | Brief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFRCOX inhibition are justified. pSrc is a potential resistance biomarker for antiEGFR therapy, and warrants investigation as a molecular target. |