University of Pittsburgh Cancer Institute (UPCI)

Window-of-Opportunity Platform Trials

Clinical StudiesHNCP members have developed a robust neoadjuvant or “window-of-opportunity” clinical trial platform to anchor the program's clinical-translational science. In an HNC window trial, patients intended for primary surgical management undergo brief exposure to a novel anticancer drug. Specific mechanistic hypotheses are then tested in paired, pre- and post-treatment biospecimens. This approach is leading to new signaling, genomic and immune discoveries. Candidate molecular or immunotherapeutic targeting agents forwarded for neoadjuvant evaluation are identified in preclinical models in HNCP laboratories.

Selected Publications

  • 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. A randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo was conducted in patients with untreated, operable stage II-IVb HNSCC. Results indicated that brief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR-COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target. (Gross et. al., Clin Cancer Res. 2014 Jun 15;20(12):3289-98.)
  • In the same window trial, the modulation of serum proteins was examined after neoadjuvant treatment with erlotinib with or without sulindac in head and neck cancer patients. Several analytes were significantly altered (generally decreased) post-treatment, in patients who received erlotinib (with or without sulindac) as well as in the placebo groups. No single analyte was differentially altered across the three treatment groups. Single HGF ELISA suggested a nonspecific decrease in all patients. These results demonstrate the importance of a placebo group when assessing changes in expression of serum biomarkers. While multiplex platforms can provide quantitative information on a large number of serum analytes, results should be cautiously compared across platforms due to their intrinsic features. Furthermore, the dynamic range of expression of a single analyte is constrained in multiplex versus standard ELISA. (Moskowitz et. al., Oral Oncol. 2012 Nov;48(11):1136-45.)

Members

Chiosea, Simion, MD, FASCP
Pathology
Gooding, William, MS
Biostatistics
Clump, David, MD, PhD
Radiation Oncology
Heron, Dwight, MD, FACRO
Radiation Oncology
Duvvuri, Umamaheswar, MD, PhD, FACS
Otolaryngology
Johnson, Jonas, MD, FACS
Otolaryngology
Ferris, Robert L., MD, PhD, FACS
Otolaryngology
Kim, Seungwon, MD, MS, FACS
Otolaryngology